مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Polymeric Nanoparticles for Targeted Drug Delivery in Cancer Treatment
Polymeric Nanoparticles for Targeted Drug Delivery in Cancer Treatment
Asal Naghipour-Kordlar,1,*Maryam Radmanfard,2
1. Faculty of Nursing, Tabriz University of Medical Sciences, Tabriz, Iran 2. Department of Basic Sciences, Ta.C., Islamic Azad University, Tabriz, Iran
Introduction: Cancer is one of the leading causes of global morbidity and mortality. Chemotherapy, radiotherapy, and surgery remain cornerstones of treatment but are often associated with systemic toxicity, low selectivity, and multidrug resistance. Nanoparticle-based drug delivery systems (NDDSs) have emerged as a promising strategy to overcome these barriers by improving drug stability, enabling site-specific release, and minimizing systemic side effects (Abdessalem & Adham, 2024).
This review focuses on recent advances in polymeric, liposomal, metallic, mesoporous silica, and dendritic nanoparticles for targeted drug delivery, highlighting in vivo therapeutic outcomes, challenges, and translational potential.
Methods: A literature search was conducted in PubMed, Scopus, and Web of Science (2015–2025) using keywords: nanoparticles, targeted drug delivery, cancer therapy, polymeric nanoparticles, liposomes, metallic nanoparticles, mesoporous silica, dendritic nanoparticles, immunotherapy. Both preclinical and clinical studies were included, with emphasis on in vivo findings reporting efficacy, targeting, and translational perspectives.
Results: Polymeric Nanoparticles
Polymeric nanoparticles are highly versatile due to biocompatibility, structural tunability, and responsiveness to tumor-specific stimuli. In vivo studies confirm their efficacy: (Pei et al., 2025) demonstrated that glutathione (GSH)-responsive polymeric nanocarriers encapsulating doxorubicin (DOX) achieved controlled release in acidic tumor microenvironments, suppressing tumor growth while minimizing systemic leakage. Mechanistically, these platforms combined apoptosis and ferroptosis via DOX-induced hydrogen peroxide generation, mitochondrial destabilization, and GPX4 downregulation, leading to effective tumor eradication.
Liposomes
Liposomal systems are clinically validated drug carriers, widely applied in both cancer therapy and vaccines. Advances include:
• Targeted liposomes functionalized with ligands/antibodies for receptor-specific uptake.
• Stimuli-responsive liposomes engineered to release cargo under acidic pH, enzymatic activity, ultrasound, or magnetic fields.
• Combination therapy liposomes co-delivering chemotherapy with nucleic acids or immunomodulators.
In vivo studies confirmed higher tumor accumulation, reduced systemic toxicity, and synergistic immune responses (Cheng et al., 2025).
Metallic Nanoparticles
Metallic nanoparticles enhance cancer immunotherapy by releasing bioactive ions (Mn²⁺, Pt, Zn²⁺, Au³⁺). For instance, Mn²⁺ activates the cGAS–STING pathway, triggering interferon responses, while Pt nanoparticles induce immunogenic cell death (ICD) and augment phototherapy (Wang et al., 2025). Ferumoxytol, an FDA-approved iron oxide nanoparticle, reprograms tumor-associated macrophages toward an antitumor M1 phenotype in vivo. These multifunctional systems integrate drug delivery, immune modulation, and controlled release.
Mesoporous Silica Nanoparticles (MSNs)
MSNs exhibit high surface area, tunable pore size, and functionalizable surfaces. They accommodate hydrophilic and hydrophobic drugs, allowing site-specific release triggered by pH or enzymatic cues. In vivo studies show MSNs significantly enhance tumor regression while reducing systemic toxicity (Gu et al., 2024). Functionalization with immunoadjuvants further boosts anti-tumor immunity.
Dendritic Nanoparticles
Dendritic nanocarriers, such as polyethylenimine (PEI)-grafted silica nanoparticles, serve as potent nanovaccine platforms. By delivering tumor antigens and adjuvants to type 1 conventional dendritic cells (cDC1s), they enhance cross-presentation and CD8⁺ T cell activation. In vivo experiments confirm robust antitumor immune responses, mediated via STING pathway activation and macrophage polarization toward M1 phenotypes (Nguyen et al., 2024).
Table: Summary of Nanoparticle Systems in Targeted Cancer Therapy
Nanoparticle Type Key Features Mechanism of Action In Vivo Findings Limitations
Polymeric NPs Biocompatible, tunable, stimuli-responsive Encapsulation of drugs; controlled release in acidic/GSH-rich tumor microenvironment; induction of apoptosis + ferroptosis (Pei et al., 2025): DOX-loaded polymeric nanocarriers triggered apoptosis + ferroptosis, activated p53 pathway, suppressed breast tumor growth Premature drug leakage; variability in biodegradation rates
Liposomes Clinically validated, lipid bilayer, modifiable surface Passive EPR effect, ligand-based active targeting, stimuli-triggered release (Cheng et al., 2025): In vivo studies show enhanced tumor accumulation, prolonged circulation, reduced systemic toxicity Stability issues, limited large-scale reproducibility, regulatory hurdles
Metallic NPs Multifunctional, immunomodulatory metal ions (Mn²⁺, Pt, Fe³⁺, Au³⁺) ICD induction, cGAS–STING activation, macrophage polarization (M2→M1) (Wang et al., 2025): Ferumoxytol (iron oxide NPs, FDA-approved) reprogrammed TAMs to M1 phenotype, enhancing antitumor immunity in vivo Potential long-term toxicity, risk of metal accumulation
Mesoporous Silica NPs (MSNs) High surface area, tunable pore size, easily functionalized Loading of chemo/immunotherapeutics; stimuli-responsive release (pH, enzymes) (Gu et al., 2024): In vivo MSN delivery enhanced tumor regression, reduced systemic toxicity, improved immune responses Safety profile not fully established; large-scale synthesis challenges
Dendritic NPs Branched polymeric or PEI-grafted silica, high cargo capacity Nanovaccines: deliver tumor antigens/adjuvants to cDC1s; STING pathway activation (Nguyen et al., 2024): In vivo nanovaccine studies → CD8⁺ T cell activation, tumor regression, improved survival Biodistribution control, stability, and translational barriers
Discussion
Targeting Strategies
1. Passive Targeting (EPR effect): Nanoparticles (20–200 nm) accumulate in tumors due to leaky vasculature and poor lymphatic drainage (Bazak et al., 2015). In vivo models demonstrate improved circulation and therapeutic efficacy.
2. Active Targeting: Surface conjugation with ligands, antibodies, or peptides enables receptor-mediated uptake. In vivo evidence shows higher tumor uptake and reduced off-target toxicity (Bazak et al., 2015).
3. Stimuli-Responsive Systems: Designed to release drugs in response to tumor-specific conditions (low pH, redox gradients) or external triggers (light, magnetic fields). In vivo DOX-loaded pH-sensitive nanoparticles achieved significant tumor shrinkage without cardiotoxicity (Mi, 2020).
4. Controlled Release: Polymeric and mesoporous carriers sustain therapeutic levels, reduce dosing frequency, and prolong tumor suppression in murine models (Bai et al., 2022).
Benefits of Nanoparticle Delivery
• Enhanced tumor selectivity and reduced systemic side effects (Bazak et al., 2015).
• Prolonged circulation and optimized pharmacokinetics (Bai et al., 2022).
• Theranostic potential for simultaneous imaging and therapy (Sun et al., 2023).
• Consistently validated in vivo with superior tumor regression and safety compared to free drugs (Mi, 2020; Sun et al., 2023).
Challenges
• Immune clearance and opsonization limit tumor accumulation (Bai et al., 2022).
• Long-term toxicity and biocompatibility remain concerns (Mi, 2020).
• Large-scale reproducibility and regulatory approval pose significant barriers (Sun et al., 2023).
Future Perspectives
• Combination therapies integrating chemotherapy, immunotherapy, and gene therapy (Sun et al., 2023).
• Multifunctional nanoplatforms combining drug delivery, imaging, and immune modulation (Mi, 2020; Sun et al., 2023).
• AI-guided design for optimizing size, shape, and targeting (Bai et al., 2022; Sun et al., 2023).
• Clinical translation through standardized large-scale production and rigorous in vivo validation(Bai et al., 2022; Sun et al., 2023).
Conclusion: Nanoparticle-based systems have revolutionized targeted cancer therapy, offering precise delivery, controlled release, and synergistic antitumor effects. Polymeric, liposomal, metallic, mesoporous silica, and dendritic nanoparticles each provide unique advantages, supported by strong in vivo evidence. Remaining challenges include scalability, immune clearance, and regulatory barriers. Future integration of multifunctional nanoplatforms, AI-guided optimization, and combinatorial immuno-nanomedicine will accelerate clinical translation, advancing precision oncology.
Keywords: Nanoparticles, Targeted drug delivery, Cancer therapy, Stimuli-responsive nanocarriers, Precision on