Nanoparticle delivery systems are innovative platforms for skin-localized chemotherapy in the treatment of non-melanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). These common cancers often require localized treatment approaches to minimize systemic toxicity and preserve healthy skin. Nanoparticles, engineered at the nanoscale, offer unique advantages in delivering chemotherapeutic agents directly to tumor sites through enhanced skin penetration, sustained drug release, and selective targeting of cancer cells. Liposomes, polymeric nanoparticles, solid lipid nanoparticles, and dendrimers have demonstrated high efficacy in encapsulating drugs such as 5-fluorouracil, doxorubicin, and cisplatin, improving their bioavailability and therapeutic outcomes. Nanoparticle-based systems leverage passive targeting through enhanced permeability and retention (EPR) effects and can be further functionalized with ligands to achieve active targeting of overexpressed receptors on NMSC cells. These systems have shown potential in reducing off-target effects, minimizing drug degradation, and improving patient compliance compared to traditional topical or systemic therapies. Preclinical studies have highlighted the ability of nanoparticles to penetrate the stratum corneum and accumulate in tumor tissue without significant systemic absorption, emphasizing their role in localized treatment. Furthermore, the integration of nanoparticles with photodynamic and immunotherapy agents offers synergistic effects, enhancing tumor eradication and immune activation. Through utilizing localized drug delivery in NMSCs, nanoparticle-based therapies represent a promising avenue for effective, targeted treatment while minimizing adverse effects, ultimately improving outcomes for patients with these skin cancers.
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