Chitosan has emerged as a biodegradable, absorbable, non-toxic, biocompatible biopolymer for wound healing and drug delivery applications. Chitosan can be converted to nanofibers which have higher potential for wound healing and drug delivery applications as compared to chitosan nanoparticles and nanocomposites. Due to these properties chitosan nanofiber has emerged as a promising candidate for biomedical research. In the recent decades it has been observed that several studies reported about the production and medical applications of chitosan nanofibers. Although, preparation and application of chitosan nanofibers is easy. But there are several challenges and bottlenecks associated with its practical application and large-scale production. The presented review is a comprehensive discussion on the major challenges and bottlenecks associated with chitosan nanofibers synthesis and their practical applications in biomedical research. It discusses critically about the issues related to the chitosan nanofibers solubility, stability, mechanical strength, absorption and drug release properties, and its scale up hinderances. Moreover, the review presents an insight into the future recommendations on considering the parameters associated for development of an efficient, sustainable, and promising biopolymer. 

Synthesis and characterization of chitosan nanofibers for wound healing and drug delivery application

Nanoparticles as cancer therapeutic carrier fail in clinical translation due to complex biological environments in vivo consisting of electrolytes and proteins which render nanoparticle aggregation and unable to reach action site. This review identifies the desirable characteristics of nanoparticles and their constituent materials that prevent aggregation from site of administration (oral, lung, injection) to target site. Oral nanoparticles should ideally be 75-100 nm whereas the size of pulmonary nanoparticles minimally affects their aggregation. Nanoparticles generally should carry excess negative surface charges particularly in fasting state and exert steric hindrance through surface decoration with citrate, anionic surfactants and large polymeric chains (polyethylene glycol and polyvinylpyrrolidone) to prevent aggregation. Anionic as well as cationic nanoparticles are both predisposed to protein corona formation as a function of biological protein isoelectric points. Their nanoparticulate surface composition as such should confer hydrophilicity or steric hindrance to evade protein corona formation or its formation should translate into steric hindrance or surface negative charges to prevent further aggregation. Unexpectedly, smaller and cationic nanoparticles are less prone to aggregation at cancer cell interface favoring endocytosis whereas aggregation is essential to enable nanoparticles retention and subsequent cancer cell uptake in tumor microenvironment. Present studies are largely conducted in vitro with simplified simulated biological media. Future aggregation assessment of nanoparticles in biological fluids that mimic that of patients is imperative to address conflicting materials and designs required as a function of body sites in order to realize the future clinical benefits. 

Overcoming colloidal nanoparticle aggregation in biological milieu for cancer therapeutic delivery: Perspectives of materials and particle design

Although bioactive compounds (BCs) have many important functions, their applications are greatly limited due to their own defects. The development of nanocarriers (NCs) technology has gradually overcome the defects of BCs. NCs are equally important as BCs to some extent. Self-assembly (SA) methods to build NCs have many advantages than chemical methods, and SA has significant impact on the structure and function of NCs. However, the relationship among SA mechanism, structure, and function has not been given enough attention. Therefore, from the perspective of bottom-up building mechanism, the concept of SA-structure-function of NCs is emphasized to promote the development of SA-based NCs. First, the conditions and forces for occurring SA are introduced, and then the SA basis and molecular mechanism of protein, polysaccharide, and lipid are summarized. Then, varieties of the structures formed based on SA are introduced in detail. Finally, facing the defects of BCs and how to be well solved by NCs are also elaborated. This review attempts to describe the great significance of constructing artificial NCs to deliver BCs from the aspects of SA-structure-function, so as to promote the development of SA-based NCs and the wide application of BCs.

Self-Assembled Nanocarrier Delivery Systems for Bioactive Compounds.

Mild photothermal therapy (PTT) is an emerging and elegant approach with minimal adverse effects, demonstrating itself as an effective treatment for cancer. However, potential challenges may arise from the overexpression of heat shock protein 90 (HSP90) and the reliance on monotherapy. Here, a near‐infrared (NIR) light‐triggered MXene nanocomposite (FA@MXene/CuO2/GA) is developed to synergistically combine mild PTT and chemodynamic therapy (CDT) for remarkably effective tumor eradication without any notable tissue damage. Under the irradiation of NIR light, the nanocomposite effectively enhances the mild PTT by suppressing HSP90 expression through the release of gambogic acid (GA) due to the excellent photothermal performance of Ti3C2 MXene nanosheets as well as the tumor‐targeting ability and biocompatibility of the surface‐modified FA‐PEG‐SH. The copper‐based catalyst CuO2 in this system releases Cu2+ in an acid‐triggered manner within the tumor microenvironment, activating the Fenton‐like reaction to generate hydroxyl radicals, and the simultaneous production of H2O2 serves to alleviate the deficiency of endogenous H2O2 within the tumor. Overall, the current work showcases a remarkable synergistic anticancer effect of PTT and CDT, and also proposes new avenues for research in utilizing MXene nanomaterials for tumor treatment.

Near‐Infrared Light‐Triggered MXene Nanocomposite for Tumor‐Specific Mild Photothermal‐Enhanced Chemodynamic Therapy

Chitosan nanoparticles (NPs) serve as useful multidrug delivery carriers in cancer chemotherapy. Chitosan has considerable potential in drug delivery systems (DDSs) for targeting tumor cells. Doxorubicin (DOX) has limited application due to its resistance and lack of specificity. Chitosan NPs have been used for DOX delivery because of their biocompatibility, biodegradability, drug encapsulation efficiency, and target specificity. In this review, various types of chitosan derivatives are discussed in DDSs to enhance the effectiveness of cancer treatments. Modified chitosan–DOX NP drug deliveries with other compounds also increase the penetration and efficiency of DOX against tumor cells. We also highlight the endogenous stimuli (pH, redox, enzyme) and exogenous stimuli (light, magnetic, ultrasound), and their positive effect on DOX drug delivery via chitosan NPs. Our study sheds light on the importance of chitosan NPs for DOX drug delivery in cancer treatment and may inspire the development of more effective approaches for cancer chemotherapy.

Optimized DOX Drug Deliveries via Chitosan-Mediated Nanoparticles and Stimuli Responses in Cancer Chemotherapy: A Review

Functionalized chitosan for cancer nano drug delivery

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Functionalized chitosan for cancer nano drug delivery