Tumor microenvironment penetrating chitosan nanoparticles for elimination of cancer relapse and minimal residual disease

Abstract

Chitosan and its derivatives are among biomaterials with numerous medical applications, especially in cancer. Chitosan is amenable to forming innumerable shapes such as micelles, niosomes, hydrogels, nanoparticles, and scaffolds, among others. Chitosan derivatives can also bring unprecedented potential to cross numerous biological barriers. Combined with other biomaterials, hybrid and multitasking chitosan-based systems can be realized for many applications. These include controlled drug release, targeted drug delivery, post-surgery implants (immunovaccines), theranostics, biosensing of tumor-derived circulating materials, multimodal systems, and combination therapy platforms with the potential to eliminate bulk tumors as well as lingering tumor cells to treat minimal residual disease (MRD) and recurrent cancer. We first introduce different formats, derivatives, and properties of chitosan. Next, given the barriers to therapeutic efficacy in solid tumors, we review advanced formulations of chitosan modules as efficient drug delivery systems to overcome tumor heterogeneity, multi-drug resistance, MRD, and metastasis. Finally, we discuss chitosan NPs for clinical translation and treatment of recurrent cancer and their future perspective.

A rapid protocol for synthesis of chitosan nanoparticles with ideal physicochemical features

“…The stability of the manufactured NPs, in addition to other indicated critical parameters, significantly contributes to the creation of a secure and efficient drug delivery system. Among polymeric nanocarriers, Cs-based NPs are attractive due to many reasons, in particular their natural, obtainable, cheap, east synthesis, and functionality [ 15 ].…”

“…Examples of the most common NDDSs comprise metallic (e.g., silver, gold, and iron, etc.) [ [2] , [3] , [4] ], carbon-based [ 5 , 6 ], quantum dot [ 7 ], synthetic polymers (e.g., poly(lactic- co -glycolic acid) (PLGA) [ [8] , [9] , [10] , [11] , [12] ]), natural polymers like chitosan (Cs) [ [13] , [14] , [15] ], β-cyclodextrin [ 16 ], gelatin [ 17 ], bovine serum albumin [ 18 ], and lipid-based [ 19 ] (e.g., liposomes [ [20] , [21] ] and solid lipid nanoparticles (SLNs) [ [22] , [23] ]), nanoparticles (NPs), among others. Each of these NPs shows considerable characteristics as NDDSs [ 24 ], while they may own tangible weaknesses like toxicity [ 25 ], high material prices, and hard and sophisticated preparation procedures, which may be addressed by considering or altering some important factors.…”

“…Among natural biomaterials, Cs is a non-toxic, natural polymer that can address many challenges regarding suitable NP preparation. It is also an inexpensive material and can be easily found and purchased [ 15 ]. Cs (poly-(D) glucosamine) is a deacetylated extract of chitin, which can be obtained from the shell of shrimp or crab.…”

Codelivery of methotrexate and silibinin by niosome nanoparticles for enhanced chemotherapy of CT26 colon cancer cells

“…Another key feature of good NDDS is its high drug loading and potential for controlled and longterm drug release [47]. The encapsulation percentage of methotrexate in niosomal vesicles is influenced by lipid concentration, surfactant type and surfactant concentration.…”

Biomaterials-mediated CRISPR/Cas9 delivery: recent challenges and opportunities in gene therapy

“…Chitosan hydrogels or films, which may be loaded with CRISPR/Cas9 components and delivered directly to target tissues or cells, are a different strategy. These formulations can enhance the bioavailability and retention of the gene editing components and offer a prolonged release of those components ( Mahmudi et al, 2022 ).…”