Recent advances in engineering chitosan-based nanoplatforms in biotherapeutic multi-delivery for multi-targeted disease treatments: Promises and outlooks

A novel cancer treatment that overcomes drug resistance, bioavailability, and systemic toxicity using nanocarrier technologies to deliver chemotherapeutic drugs and nucleic acids, is a multi-delivery strategy. In recent preclinical trials of multidrug-resistant malignancies, chitosan-based nanoparticles reduced tumors (doxorubicin (DOX) + survivin siRNA and curcumin + siRNA). Folate-chitosan-paclitaxel/miR-200c co-delivery trials have increased ovarian cancer patients' disease-free survival up to ∼5 months. Researchers have developed liposomes, polymeric nanoparticles, dendrimers, micelles, and inorganic nanoparticles to secure cargo, ensure proper release, and improve tumor targeting. The absorption of ligands and pH- or redox-responsive components in HepG2 cells has increased. Fluorescence spectroscopy and flow cytometry are applied to quantify cellular uptake and monitor intracellular drug release, while inductively coupled plasma mass spectrometry (ICP-MS) can be used for precise quantification of inorganic nanoparticle content within cells. Chitosan-based intelligent systems like TAT-C-SS-P significantly reduce IL-6 levels and tumor incidence by 80 % ( p < 0.001). Despite these advances, clinical translation still struggles to obtain regulatory approval, ensure consistent results, and scale. Over 23 clinical trials using chitosan nanoparticles are underway or completed. Their initial studies reveal low toxicity and long-term medication delivery. Tailored nanomedicines that can accurately control the release of multiple drugs over time and space are essential for co-delivery systems.