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Chitosan Nanoparticles for Targeted Cancer Therapy: A Review of Stimuli-Responsive, Passive, and Active Targeting
Jafar R M H Al-Shadidi1, Shahad Al-Shammari1, Danah Al-Mutairi1
1Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates.
Abstract:
Despite all major advancements in drug discovery and development in the pharmaceutical industry, cancer is still one of the most arduous challenges for the scientific community. The implications of nanotechnology have certainly resolved major issues related to conventional anticancer modalities; however, the undesired recognition of nanoparticles (NPs) by the mononuclear phagocyte system (MPS), their poor stability in biological fluids, premature release of payload, and low biocompatibility have restricted their clinical translation. In recent decades, chitosan (CS)-based nanodelivery systems (eg, polymeric NPs, micelles, liposomes, dendrimers, conjugates, solid lipid nanoparticles, etc.) have attained promising recognition from researchers for improving the pharmacokinetics and pharmacodynamics of chemotherapeutics. However, the specialty of this review is to mainly focus on and critically discuss the targeting potential of various CS-based NPs for treatment of different types of cancer. Based on their delivery mechanisms, we classified CS-based NPs into stimuli-responsive, passive, or active targeting nanosystems. Moreover, various functionalization strategies (eg, grafting with polyethylene glycol (PEG), hydrophobic substitution, tethering of stimuli-responsive linkers, and conjugation of targeting ligands) adapted to the architecture of CS-NPs for target-specific delivery of chemotherapeutics have also been considered. Nevertheless, CS-NPs based therapeutics hold great promise for improving therapeutic outcomes while mitigating the off-target effects of chemotherapeutics, a long-term safety profile and clinical testing in humans are warranted for their successful clinical translation.
Insights
Chitosan-based nanoparticles show promise for targeted cancer therapy by improving drug delivery. Further research is needed to ensure their safety and efficacy for clinical translation.
Area of Science:
- Nanotechnology and Materials Science
- Oncology and Pharmaceutical Sciences
Background:
- Cancer remains a significant challenge despite pharmaceutical advancements.
- Conventional nanomedicines face limitations like immune system recognition, instability, premature drug release, and poor biocompatibility, hindering clinical use.
- Chitosan (CS)-based nanodelivery systems offer potential for enhancing chemotherapeutic pharmacokinetics and pharmacodynamics.
Purpose of the Study:
- To critically review the targeting potential of various chitosan-based nanoparticles (CS-NPs) for diverse cancer treatments.
- To classify CS-based NPs based on their drug delivery mechanisms.
- To examine functionalization strategies for CS-NPs to achieve targeted drug delivery.
Main Methods:
- Classification of CS-based NPs into stimuli-responsive, passive, or active targeting nanosystems based on delivery mechanisms.
- Analysis of functionalization strategies including polyethylene glycol (PEG) grafting, hydrophobic substitution, stimuli-responsive linker tethering, and targeting ligand conjugation.
- Review of existing literature on CS-NP applications in cancer therapy.
Main Results:
- CS-based NPs demonstrate potential for improving therapeutic outcomes in cancer treatment.
- Functionalization strategies enhance the target-specific delivery of chemotherapeutics via CS-NPs.
- Different targeting mechanisms (passive, active, stimuli-responsive) are employed by CS-NPs.
Conclusions:
- CS-NPs hold significant promise for advancing cancer therapeutics by improving efficacy and reducing side effects.
- Targeted delivery via functionalized CS-NPs can mitigate off-target effects of chemotherapeutics.
- Long-term safety evaluation and human clinical trials are essential for the successful clinical translation of CS-NP-based therapies.
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