1. Introduction

Cancer is one of the most serious global health crises of our era, posing tremendous challenges in treatment strategies because of the high side effects of existing therapeutic modalities and the intrinsic difficulties in achieving specific tumor targeting. Conventional chemotherapy protocols, although effective at eradicating malignant cells, act through mechanisms that non-selectively impact both cancerous and normal rapidly proliferating cells, thereby inducing intense systemic toxicity that often restricts treatment efficacy and impairs patient quality of life. The lack of selectivity of anticancer agents results in catastrophic side effects such as bone marrow suppression, gastrointestinal toxicity, cardiotoxicity, and neurotoxicity that often require dose reduction or treatment interruption, with an inevitable impairment of therapeutic results [1].

The underlying challenge for cancer treatment is the poor targeting capacity of current pharmaceutical drugs, which fail to deliver precisely to tumor tissues and spare normal tissues. The reason for this shortcoming is the absence of specificity in drug delivery mechanisms [2], wherein therapeutic drugs circulate throughout the body and distribute into malignant and normal tissues largely according to passive distribution profiles instead of selective targeting processes. The subsequent therapeutic window between efficacy and toxicity tends to be small, demanding fine balance between delivery of adequate drug levels at tumor locations and reduction of exposure to normal organs [3]. Nanotechnology has appeared as a groundbreaking strategy to overcome these inherent limitations in cancer treatment, providing unprecedented potential to create advanced drug delivery systems that can transcend the limitations of conventional chemotherapy. By the exact engineering of nanoscale drug carriers with meticulously tailored structures and functions, researchers are now able to design delivery platforms that greatly minimize necessary drug dosages while concomitantly strengthening specific targeting potential to cancerous tissues. These sophisticated nanocarrier platforms allow for the combination of several therapeutic functions into individual platforms, such as assisted imaging diagnosis, real-time drug distribution monitoring, and controlled release mechanisms that are triggered by specific conditions of the tumor microenvironment.

At the sizes from 1 to 100 nanometers, materials possess distinct physicochemical properties that are vastly different from their bulk analogs, with different optical, magnetic, electrical, and mechanical properties that can be engineered precisely for individual therapeutic purposes. The technology and science of nanotechnology deal with producing materials from individual atoms or molecules, allowing for unprecedented material control and interaction with biology [4].

Cancer therapy drugs have varied mechanisms of action but are mainly comprised of agents that impact DNA structure and function, drugs that inhibit nucleic acid biosynthetic pathways, anti-mitotic agents that interfere with cellular division mechanisms, and targeted therapies relying on the specific tumor cell signal transduction pathways. The combination of these different therapeutic approaches with sophisticated nanocarrier platforms facilitates the formulation of combination therapy strategies with the potential to impact multiple facets of cancer pathophysiology concurrently with a diminished potential for the development of resistance.

The role of nanocarrier technology in cancer therapy goes beyond the mere improvement of drug delivery to involve basic shifts in the way we consider cancer treatment. The systems have the potential to bring personalized medicine strategies to cancer treatment by allowing for the tailoring of therapy to specific patient characteristics, tumor biology, and therapeutic history. Co-delivery of multiple therapeutic agents, imaging contrast agents, and targeting molecules in single nanocarrier platforms is possible and offers the potential for integrated treatment approaches that account for the complicated and heterogeneous nature of cancer while reducing systemic toxicity and enhancing patient outcomes.

2. Nanocarrier material selection

The selection of appropriate nanocarrier materials represents a critical determinant of therapeutic success, requiring comprehensive evaluation of multiple factors including biocompatibility, drug loading capacity, targeting efficiency, release kinetics, and manufacturing feasibility. Nanocarrier materials are fundamentally categorized into two primary classes: organic materials and inorganic materials, each exhibiting distinct advantages and limitations that must be carefully considered in the context of specific therapeutic applications. These material classes demonstrate significant differences in synthesis processes [5], structural characteristics, physicochemical properties, and biological interactions, necessitating systematic analysis to guide rational material selection for anticancer drug delivery applications.

2.1. Organic nanomaterials

Organic nanomaterials have established themselves as the predominant class of nanocarriers in anticancer drug delivery applications, primarily due to their exceptional biocompatibility profiles, inherent biodegradability characteristics, and remarkable ease of functionalization and surface modification. These materials offer unique advantages in terms of biological safety and regulatory acceptance, having demonstrated successful clinical translation with multiple formulations already approved for cancer therapy [6]. The organic nanocarrier category encompasses a diverse range of material types, including sophisticated polymeric materials, naturally derived proteins, and biomimetic liposomal systems, each offering distinct advantages for specific therapeutic applications. Polymeric materials represent the most versatile and widely studied class of organic nanocarriers, offering unprecedented opportunities for customization and optimization of drug delivery properties. Amphiphilic polymers constitute a particularly important subclass of polymeric materials, characterized by their unique molecular architecture that incorporates both hydrophilic and hydrophobic segments within single polymer chains. These specialized polymers demonstrate remarkable self-assembly capabilities, spontaneously organizing into well-defined micellar structures or nanoparticles when exposed to aqueous environments. The hydrophobic core regions of these self-assembled structures provide ideal environments for encapsulating poorly water-soluble anticancer drugs, while the hydrophilic outer shells ensure colloidal stability and biocompatibility in physiological conditions. The critical micelle concentration of amphiphilic polymers can be precisely controlled through molecular design, enabling optimization of stability under dilution conditions encountered during systemic circulation. Dendrimers represent another fascinating class of polymeric nanomaterials, distinguished by their highly branched, tree-like molecular structures that radiate outward from central core units through successive generations of branching points [7]. These unique architectural features result in globular macromolecules with well-defined molecular weights, uniform sizes, and numerous terminal functional groups that can be precisely modified for specific applications. The controlled synthesis of dendrimers enables exact determination of molecular composition and structure, providing unprecedented reproducibility in nanocarrier properties. The abundant terminal functional groups facilitate extensive modification with targeting ligands, therapeutic agents, and imaging contrast agents, enabling the development of multifunctional theranostic platforms. The internal cavities and surface functional groups of dendrimers provide multiple mechanisms for drug association, including encapsulation within internal voids, complexation with functional groups, and covalent conjugation to terminal sites.

Hydrogels represent three-dimensional cross-linked network structures composed of hydrophilic polymers that can absorb substantial amounts of water while maintaining structural integrity. These materials offer unique advantages for sustained drug release applications, as their porous network structures enable controlled diffusion of therapeutic agents over extended time periods. The cross-linking density and polymer composition can be precisely controlled to achieve desired release kinetics, ranging from immediate release to sustained release over weeks or months. Advanced hydrogel systems incorporate stimuli-responsive elements that enable triggered drug release in response to specific environmental conditions such as pH changes, temperature variations, or enzymatic activity. The biocompatibility of hydrogels stems from their high water content and soft, tissue-like mechanical properties that minimize inflammatory responses and foreign body reactions.

Protein-based nanocarriers leverage the inherent biocompatibility and biodegradability of naturally occurring proteins while offering unique targeting capabilities through specific receptor recognition mechanisms. Albumin represents the most extensively studied protein carrier, demonstrating exceptional safety profiles due to its natural abundance in human plasma and well-characterized metabolism pathways. Human serum albumin nanoparticles can be loaded with hydrophobic drugs through non-covalent binding mechanisms, providing stable drug association while enabling controlled release through competitive displacement or enzymatic degradation. Transferrin represents another important protein carrier that exploits the increased iron requirements of rapidly proliferating cancer cells, which upregulate transferrin receptor expression to facilitate iron uptake. Transferrin-based nanocarriers undergo receptor-mediated endocytosis, enabling efficient intracellular drug delivery while bypassing drug efflux mechanisms that contribute to multidrug resistance [8].

Liposomal systems represent biomimetic nanocarriers composed of phospholipid bilayers that closely resemble natural cell membrane structures, providing exceptional biocompatibility and low immunogenicity profiles. The phospholipid bilayer architecture enables encapsulation of both hydrophilic drugs within the aqueous core and hydrophobic drugs within the lipid bilayer, offering versatility in drug loading capabilities. The composition of liposomal membranes can be precisely controlled through selection of phospholipid types, cholesterol content, and surface modification agents, enabling optimization of stability, circulation time, and targeting properties. Stealth liposomes incorporate polyethylene glycol chains on their surface to reduce recognition by the reticuloendothelial system, significantly extending circulation half-life and enhancing tumor accumulation through passive targeting mechanisms. The clinical success of liposomal formulations, including FDA-approved products such as Doxil and DaunoXome, demonstrates the translational potential of organic nanocarrier platforms.

2.2. Inorganic nanomaterials

Inorganic nanomaterials have emerged as highly promising platforms for cancer therapy applications, distinguished by their unique physicochemical properties that include exceptional stability under physiological conditions, precisely controllable morphology and size characteristics, and remarkable multifunctional capabilities that enable integration of therapeutic and diagnostic functions within single platforms. These materials offer distinct advantages over organic counterparts in terms of structural robustness, tunable optical and magnetic properties, and resistance to enzymatic degradation, making them particularly suitable for applications requiring long-term stability or specialized functionalities. The inorganic nanocarrier category encompasses diverse material types including metallic nanomaterials, carbon-based materials, and silicon-based systems, each offering unique properties and applications in anticancer drug delivery.

Metallic nanomaterials represent a particularly important class of inorganic nanocarriers, offering unique combinations of biocompatibility, surface modification capabilities, and specialized therapeutic functionalities that are not achievable with organic materials. Gold nanoparticles have established themselves as the most extensively studied metallic nanocarriers, demonstrating exceptional biocompatibility profiles, remarkable ease of surface modification through well-established thiol chemistry, and unique optical properties that enable diverse therapeutic and diagnostic applications. The surface plasmon resonance characteristics of gold nanoparticles can be precisely tuned through control of particle size, shape, and surface modifications, enabling applications across wavelength ranges from 500 to 1200 nanometers. This tunability enables optimization for specific applications including photothermal therapy, where near-infrared light absorption generates localized heating for selective tumor destruction, photodynamic therapy applications that utilize light-activated drug release mechanisms, and advanced imaging modalities including photoacoustic imaging and computed tomography contrast enhancement. The biocompatibility of gold nanoparticles has been extensively validated through comprehensive in vitro and in vivo studies, demonstrating minimal cytotoxicity at therapeutic concentrations and acceptable safety profiles for clinical applications. Surface functionalization of gold nanoparticles with targeting ligands such as antibodies, peptides, or small molecules enables specific recognition of cancer cell surface receptors, significantly improving drug delivery efficiency while reducing off-target effects. The strong gold-sulfur bond formation enables stable conjugation of thiolated ligands and therapeutic agents, providing robust attachment that maintains stability under physiological conditions while enabling controlled release through competitive displacement or reductive cleavage mechanisms.

Carbon nanomaterials represent a revolutionary class of inorganic nanocarriers characterized by their unique structural properties and exceptional surface chemistry characteristics that enable diverse applications in drug delivery and cancer therapy. Carbon nanotubes, available in both single-walled and multi-walled configurations, possess extraordinary mechanical strength with Young's modulus values exceeding 1 terepascal, making them ideal for applications requiring structural integrity under demanding physiological conditions. The exceptional aspect ratio of carbon nanotubes, with lengths often exceeding diameters by factors of 1000 or more, facilitates cellular uptake through specialized endocytosis pathways while providing protected internal spaces for drug encapsulation and delivery. The hollow interior structure of carbon nanotubes provides unique opportunities for drug loading and protection, enabling encapsulation of therapeutic agents within the nanotube cavity where they are shielded from enzymatic degradation and premature release. Surface functionalization of carbon nanotubes with carboxyl, amino, or hydroxyl groups enhances water solubility and biocompatibility while enabling conjugation with therapeutic molecules, targeting ligands, and imaging agents. The extensive π-electron system of carbon nanotubes enables strong π-π stacking interactions with aromatic drug molecules, providing stable drug association mechanisms that can be controlled through competitive displacement or pH-mediated release strategies. Graphene and graphene oxide represent two-dimensional carbon nanomaterials with distinct properties that make them suitable for different aspects of cancer therapy applications. Pristine graphene exhibits exceptional electrical and thermal conductivity characteristics, making it particularly suitable for photothermal therapy applications where localized heating can selectively destroy cancer cells while sparing healthy tissues. The excellent thermal conductivity of graphene enables efficient heat dissipation and precise temperature control during photothermal treatments, reducing the risk of overheating and thermal damage to surrounding healthy tissues.

Graphene oxide demonstrates superior water dispersibility and biocompatibility compared to pristine graphene, attributed to the abundant oxygen-containing functional groups including carboxyl, hydroxyl, and epoxy groups distributed across the graphene surface. These functional groups provide numerous sites for chemical modification and drug conjugation while enhancing interactions with biological systems through hydrogen bonding and electrostatic interactions. The large surface area of graphene-based materials, typically exceeding 2600 square meters per gram, provides extensive space for drug adsorption through multiple interaction mechanisms including π-π stacking interactions, hydrogen bonding, and electrostatic interactions.

Silicon-based nanomaterials, particularly mesoporous silica nanoparticles, have gained significant attention in the nanocarrier field due to their exceptional pore structure tunability and outstanding biocompatibility characteristics. The sol-gel synthesis process employed for mesoporous silica nanoparticle production allows precise control over pore size distributions, typically ranging from 2 to 50 nanometers, enabling selective loading of drugs with different molecular weights and sizes. The uniform pore structures and high surface areas, often exceeding 1000 square meters per gram, provide exceptional drug loading capacities while maintaining structural integrity under physiological conditions.

The surface silanol groups present on mesoporous silica nanoparticles can be readily modified with various functional groups through well-established silane chemistry, facilitating targeted delivery applications and controlled release mechanisms. The biodegradability of silica nanoparticles in physiological conditions occurs primarily through hydrolysis reactions that convert the silica matrix to silicic acid, which is safely eliminated from the body through renal excretion pathways without long-term accumulation in organs. This biodegradation process can be controlled through surface modifications and particle size optimization, enabling tailored clearance kinetics that match therapeutic requirements while ensuring patient safety.

2.3. Hybrid and composite nanomaterials

The combination of organic and inorganic components in hybrid nanomaterials offers synergistic advantages that overcome the limitations of individual material classes. These hybrid systems can integrate the biocompatibility and biodegradability of organic materials with the stability and multifunctionality of inorganic components, creating sophisticated drug delivery platforms with enhanced therapeutic efficacy.

Lipid-coated inorganic nanoparticles represent a prominent class of hybrid materials where the inorganic core provides stability and functionality while the lipid shell ensures biocompatibility and prolonged circulation time. The lipid coating can be composed of phospholipids, cholesterol, and polyethylene glycol derivatives, creating a biomimetic surface that reduces recognition by the reticuloendothelial system. This stealth effect significantly extends the circulation half-life of nanoparticles, allowing for enhanced accumulation in tumor tissues through the enhanced permeability and retention effect.

Polymer-inorganic hybrid nanoparticles combine the targeting capabilities of functionalized polymers with the imaging and therapeutic properties of inorganic cores. For example, polymer-coated quantum dots enable simultaneous drug delivery and real-time tracking of therapeutic distribution within the body. The polymer shell can be designed to respond to specific tumor microenvironment conditions such as pH, temperature, or enzymatic activity, triggering controlled drug release at the target site.

Core-shell architectures represent another important category of hybrid nanomaterials where the core material provides the primary therapeutic function while the shell material controls surface properties and drug release kinetics. Iron oxide nanoparticles coated with biodegradable polymers combine magnetic targeting capabilities with controlled drug release, enabling magnetically guided delivery to specific anatomical locations. The magnetic properties also enable hyperthermia treatment through alternating magnetic field application, providing dual therapeutic modalities within a single platform.

Manufacturing scalability and cost considerations become increasingly important as nanomedicine platforms progress toward clinical translation. Synthesis methods must be reproducible, scalable, and compliant with good manufacturing practice standards. The complexity of multi-step synthesis procedures, requirement for specialized equipment, and raw material costs all influence the commercial viability of nanocarrier platforms.

Quality control and characterization requirements for nanomaterials are more stringent than traditional pharmaceutical formulations due to the complex relationship between physicochemical properties and biological behavior. Critical quality attributes include particle size distribution, surface charge, morphology, drug loading efficiency, and release kinetics, all of which must be monitored throughout the manufacturing process to ensure batch-to-batch consistency.

3. Comparative analysis and clinical applications

The selection of optimal nanocarrier materials for specific cancer therapy applications requires systematic comparison of material properties, therapeutic efficacy, and clinical feasibility. This section provides comprehensive analysis of different material classes and their performance in various cancer treatment modalities, supported by clinical evidence and emerging applications.

The therapeutic performance of nanocarrier materials varies significantly based on their physicochemical properties, biological interactions, and compatibility with different drug molecules. A systematic comparison reveals distinct advantages and limitations for each material class, guiding rational selection for specific applications.

Liposomes demonstrate the most favorable clinical translation profile, with multiple formulations already approved for cancer therapy including Doxil (pegylated liposomal doxorubicin) and DaunoXome (liposomal daunorubicin). The excellent biocompatibility profile stems from their biomimetic phospholipid composition, which closely resembles natural cell membranes. However, their drug loading capacity is limited by the aqueous core volume and lipid bilayer thickness, restricting applications to highly potent therapeutic agents.

Polymeric micelles offer superior targeting capabilities through precise functionalization with targeting ligands and stimuli-responsive elements. The amphiphilic nature of block copolymers enables self-assembly into stable micellar structures with hydrophobic cores suitable for poorly water-soluble drugs. The critical micelle concentration determines stability under dilution conditions encountered in vivo, with values typically ranging from 10⁻⁶ to 10⁻⁷ M for clinically relevant formulations. Advanced polymeric systems incorporate pH-sensitive, temperature-sensitive, or enzyme-cleavable linkages that enable triggered drug release in response to tumor microenvironment conditions.

Gold nanoparticles provide unique opportunities for theranostic applications combining therapy and diagnostics within a single platform. The surface plasmon resonance properties enable optical imaging, photothermal therapy, and photoacoustic imaging, while the high atomic number provides contrast for computed tomography imaging. Surface functionalization with thiolated ligands enables stable conjugation of targeting molecules and therapeutic agents through gold-sulfur bonds. The non-biodegradable nature of gold requires careful consideration of long-term safety and clearance mechanisms, particularly for repeated dosing regimens.

Mesoporous silica nanoparticles excel in controlled drug release applications due to their tunable pore structures and surface chemistry. The high surface area, typically 500-1000 m²/g, enables exceptional drug loading capacities while maintaining structural integrity. Pore size can be precisely controlled during synthesis through template selection, enabling size-selective drug loading and release. Surface functionalization with gatekeepers such as polymer chains, nanoparticles, or biomolecules enables stimuli-responsive release mechanisms triggered by pH changes, enzymatic activity, or competitive binding.

Carbon nanotubes offer the highest drug loading capacities among all nanocarrier materials due to their hollow interior structure and extensive surface area. The strong π-π interactions between aromatic drug molecules and the carbon nanotube surface provide stable drug association while enabling controlled release through competitive displacement or pH-mediated desorption. However, concerns regarding long-term biocompatibility and potential inflammatory responses have limited clinical translation, requiring extensive surface functionalization to improve biological compatibility.

3.1. Targeted drug delivery applications

The development of targeted nanocarrier systems has revolutionized cancer therapy by enabling selective delivery of therapeutic agents to malignant tissues while minimizing systemic toxicity. Different targeting strategies have been developed to exploit unique characteristics of cancer cells and the tumor microenvironment.

Passive targeting through the enhanced permeability and retention effect remains the most widely utilized approach for nanocarrier accumulation in solid tumors. The leaky vasculature and impaired lymphatic drainage characteristic of many solid tumors enable preferential extravasation and retention of nanoparticles within the tumor interstitium. Optimal particle size for passive targeting typically ranges from 50-200 nm, balancing extravasation efficiency with circulation time and cellular uptake. Surface modification with polyethylene glycol or other hydrophilic polymers creates a stealth coating that reduces protein adsorption and macrophage recognition, extending circulation half-life from minutes to hours or days.

Active targeting strategies involve surface modification with ligands that specifically recognize and bind to overexpressed receptors on cancer cells. Folate receptor targeting has been extensively studied due to the high expression levels in many cancer types including ovarian, breast, and lung cancers, with low expression in normal tissues. Folate-conjugated nanocarriers demonstrate 10-100 fold higher cellular uptake compared to non-targeted formulations, translating to improved therapeutic efficacy and reduced systemic toxicity in preclinical models.

Transferrin receptor targeting exploits the increased iron requirements of rapidly proliferating cancer cells, which upregulate transferrin receptor expression to facilitate iron uptake. Transferrin-conjugated nanocarriers undergo receptor-mediated endocytosis, enabling efficient intracellular drug delivery while avoiding drug efflux mechanisms that contribute to multidrug resistance. The natural trafficking pathway of transferrin receptors through early endosomes, recycling endosomes, and eventual lysosomal degradation provides opportunities for controlled intracellular drug release.

Antibody-targeted nanocarriers represent the most specific targeting approach, utilizing monoclonal antibodies or antibody fragments that recognize unique tumor-associated antigens. HER2-targeted nanocarriers have shown particular promise in breast cancer treatment, where HER2 overexpression occurs in approximately 20-25% of cases. The high binding affinity and specificity of antibodies enable selective targeting even in the presence of circulating soluble antigens, though the large size and potential immunogenicity of full antibodies may limit clinical applications.

Peptide-based targeting offers advantages of small size, synthetic accessibility, and reduced immunogenicity compared to antibody-based systems. Cell-penetrating peptides such as TAT, penetratin, and arginine-rich peptides facilitate cellular uptake through multiple mechanisms including direct translocation, endocytosis, and membrane disruption. Tumor-homing peptides identified through phage display screening recognize specific receptors overexpressed in tumor vasculature or cancer cells, enabling selective accumulation in malignant tissues.

3.2. Combination therapy applications

The integration of multiple therapeutic modalities within single nanocarrier platforms enables synergistic treatment effects while reducing the complexity of combination therapy regimens. These multifunctional systems can simultaneously deliver chemotherapy drugs, photosensitizers, immunomodulators, and imaging agents, creating comprehensive treatment platforms that address multiple aspects of cancer pathophysiology.

Chemo-photodynamic therapy combinations utilize nanocarriers to co-deliver chemotherapy drugs and photosensitizers, enabling sequential or simultaneous treatment modalities. The photosensitizer generates reactive oxygen species upon light activation, causing direct cellular damage while also enhancing chemotherapy drug uptake through membrane permeabilization. Liposomal formulations containing both doxorubicin and photosensitizers have demonstrated synergistic cytotoxicity in vitro and improved tumor control in animal models compared to individual treatments.

Chemo-immunotherapy combinations represent an emerging area where nanocarriers deliver both cytotoxic agents and immunomodulatory molecules to enhance anti-tumor immune responses. The immunogenic cell death induced by certain chemotherapy drugs can be enhanced through co-delivery of immune checkpoint inhibitors, cytokines, or adjuvants. Nanoparticle-mediated delivery enables precise control over the timing and location of immune activation, potentially reducing systemic immune-related adverse events while enhancing therapeutic efficacy.

Photothermal-chemotherapy combinations exploit the heat-sensitizing effects of hyperthermia to enhance chemotherapy drug efficacy. Gold nanoparticles or carbon-based materials provide photothermal conversion capabilities while simultaneously serving as drug carriers. The mild hyperthermia generated through near-infrared light activation increases membrane permeability, enhances drug release, and sensitizes cells to chemotherapy-induced apoptosis. Temperature-sensitive liposomes can be designed to release their drug payload specifically at hyperthermic temperatures, providing spatial and temporal control over drug delivery.

Gene therapy combinations utilize nanocarriers to co-deliver therapeutic genes alongside traditional anticancer agents. Small interfering RNA targeting drug resistance genes can be combined with chemotherapy drugs to overcome multidrug resistance mechanisms. The nanocarrier provides protection for nucleic acids against enzymatic degradation while facilitating cellular uptake and endosomal escape necessary for gene silencing activity. Cationic polymers and lipids are particularly suitable for nucleic acid delivery due to their ability to condense negatively charged genetic material and facilitate membrane interaction.

3.3. Personalized medicine applications

The heterogeneity of cancer at the molecular, cellular, and tissue levels necessitates personalized treatment approaches that account for individual patient characteristics, tumor biology, and treatment history. Nanocarrier platforms offer unique opportunities for personalized medicine through customizable targeting, drug selection, and dosing strategies based on patient-specific factors.

Biomarker-guided nanocarrier selection enables matching of targeting strategies to individual tumor characteristics. Patients with high folate receptor expression can benefit from folate-targeted nanocarriers, while those with HER2-positive tumors may respond better to HER2-targeted formulations. Companion diagnostic tests can identify optimal candidates for specific nanocarrier therapies, improving treatment outcomes while reducing unnecessary exposure to ineffective treatments.

Pharmacogenomic considerations play important roles in nanocarrier therapy optimization, as genetic variations in drug metabolism, transport, and target proteins influence therapeutic response. Polymorphisms in cytochrome P450 enzymes affect the metabolism of many anticancer drugs, requiring dose adjustments to maintain therapeutic concentrations while avoiding toxicity. Nanocarrier formulations can provide more consistent drug exposure profiles that are less dependent on individual metabolic variations, potentially reducing the impact of pharmacogenomic differences on treatment outcomes.

Tumor microenvironment characteristics vary significantly between patients and tumor types, influencing nanocarrier accumulation and drug release patterns. Tumors with high interstitial fluid pressure may limit nanoparticle penetration, while those with extensive fibrotic stroma may impede drug distribution. Advanced imaging techniques including magnetic resonance imaging, positron emission tomography, and optical imaging can assess tumor vascular permeability, perfusion, and microenvironment characteristics to guide nanocarrier selection and dosing strategies.

Treatment history and prior therapy responses provide valuable information for nanocarrier therapy selection. Patients who have developed resistance to specific chemotherapy agents may benefit from nanocarrier formulations that bypass resistance mechanisms through altered cellular uptake pathways, subcellular targeting, or combination with resistance modulators. The ability to co-deliver multiple agents within single nanocarrier platforms enables rational combination therapy design based on individual resistance profiles and tumor characteristics.

4. Conclusion

The selection of appropriate materials for nanocarrier-based anticancer drug delivery systems represents a critical determinant of therapeutic success, requiring careful consideration of multiple factors including biocompatibility, drug loading capacity, targeting efficiency, and manufacturing feasibility. This comprehensive analysis of organic, inorganic, and hybrid nanomaterials reveals distinct advantages and limitations for each material class, providing guidance for rational material selection based on specific therapeutic requirements. Organic nanomaterials, including liposomes, polymeric micelles, and protein-based carriers, offer excellent biocompatibility and biodegradability profiles that have facilitated successful clinical translation. The FDA approval of multiple liposomal formulations demonstrates the clinical viability of organic nanocarriers, while ongoing development of stimuli-responsive polymeric systems promises enhanced targeting and controlled release capabilities. Hybrid and composite nanomaterials represent the most promising approach for next-generation drug delivery systems, combining the advantages of organic and inorganic components while minimizing individual limitations. The integration of targeting ligands, stimuli-responsive elements, and imaging agents within single platforms enables personalized treatment approaches that account for individual patient characteristics and tumor biology. The comparative analysis presented in this study reveals that material selection must be tailored to specific applications, with no single material class optimal for all therapeutic scenarios. Liposomes remain the gold standard for clinical applications requiring proven safety and regulatory acceptance, while polymeric systems offer superior customization capabilities for specialized targeting requirements. Inorganic nanomaterials excel in applications requiring high drug loading, structural stability, or multifunctional capabilities, despite facing greater regulatory challenges.

The successful translation of nanocarrier technologies to clinical practice requires continued collaboration between materials scientists, biomedical engineers, clinicians, and regulatory agencies. Standardization of characterization methods, development of predictive models for biological behavior, and establishment of clear regulatory pathways will accelerate the development process while ensuring patient safety. The material selection principles and comparative analysis presented in this study provide a foundation for rational nanocarrier design and development. By understanding the strengths and limitations of different material classes, researchers can make informed decisions that accelerate the translation of promising technologies from laboratory research to clinical applications, ultimately improving outcomes for cancer patients worldwide.