Abstract Green chemistry has been a growing multidisciplinary field in recent years showing great promise in biomedical applications, especially for cancer therapy. Chitosan (CS) is an abundant biopolymer derived from chitin and is present in insects and fungi. This polysaccharide has favorable characteristics, including biocompatibility, biodegradability, and ease of modification by enzymes and chemicals. CS‐based nanoparticles (CS‐NPs) have shown potential in the treatment of cancer and other diseases, affording targeted delivery and overcoming drug resistance. The current review emphasizes on the application of CS‐NPs for the delivery of a chemotherapeutic agent, doxorubicin (DOX), in cancer therapy as they promote internalization of DOX in cancer cells and prevent the activity of P‐glycoprotein (P‐gp) to reverse drug resistance. These nanoarchitectures can provide co‐delivery of DOX with antitumor agents such as curcumin and cisplatin to induce synergistic cancer therapy. Furthermore, co‐loading of DOX with siRNA, shRNA, and miRNA can suppress tumor progression and provide chemosensitivity. Various nanostructures, including lipid‐, carbon‐, polymeric‐ and metal‐based nanoparticles, are modifiable with CS for DOX delivery, while functionalization of CS‐NPs with ligands such as hyaluronic acid promotes selectivity toward tumor cells and prevents DOX resistance. The CS‐NPs demonstrate high encapsulation efficiency and due to protonation of amine groups of CS, pH‐sensitive release of DOX can occur. Furthermore, redox‐ and light‐responsive CS‐NPs have been prepared for DOX delivery in cancer treatment. Leveraging these characteristics and in view of the biocompatibility of CS‐NPs, we expect to soon see significant progress towards clinical translation.

Chitosan‐based nanoscale systems for doxorubicin delivery: Exploring biomedical application in cancer therapy

Antisense oligonucleotides (ASOs) are an important tool for the treatment of many genetic disorders. However, similar to other gene drugs, vectors are often required to protect them from degradation and clearance, and to accomplish their transport in vivo. Compared with viral vectors, artificial nonviral nanoparticles have a variety of design, synthesis, and formulation possibilities that can be selected to accomplish protection and delivery for specific applications, and they have served critical therapeutic purposes in animal model research and clinical applications, allowing safe and efficient gene delivery processes into the target cells. We believe that as new ASO drugs develop, the exploration for corresponding nonviral vectors is inevitable. Intensive development of nonviral vectors with improved delivery strategies based on specific targets can continue to expand the value of ASO therapeutic approaches. Here, we provide an overview of current nonviral delivery strategies, including ASOs modifications, action mechanisms, and multi-carrier methods, which aim to address the irreplaceable role of nonviral vectors in the progressive development of ASOs delivery. 

/pdf/nonviral-delivery-systems-for-antisense-oligonucleotide-3mebbd45.pdf

Nonviral delivery systems for antisense oligonucleotide therapeutics

Carbon quantum dots (CQDs) were synthesized via a green, one-step hydrothermal method. As CQD precursors, nine amino acids of different structural descriptors (negatively/positively charged in water, polar, hydrophobic, sulfur-containing, and other/complex ones) were surveyed: Asp, Cys, Gly, His, Leu, Lys, Phe, Pro, and Ser. The reactions were performed in an autoclave in the presence of citric acid at 180 °C for 24 h and yielded core–shell CQDs. CQDs were comprehensively characterized by transmission electron microscopy, dynamic light scattering, Raman, UV/Vis, infrared, X-ray photoelectron spectroscopy, and fluorescence spectroscopy. At the excitation wavelength of λex = 350 nm, Cys-, Phe-, Leu-, and Lys-based CQDs displayed the highest quantum yield blue fluorescence—90 ± 5, 90 ± 4, 87 ± 5, and 67 ± 3%, respectively—superior to the conventional fluorescent dyes. Strikingly, for Lys- and Phe-CQDs, dissimilar trends in the excitation–emission wavelength relationships were identified, that is, constantly strong red shifts versus excitation wavelength-independent emission. Cys- and Lys-CQDs were water-dispersible toward the narrow unimodal distribution of hydrodynamic diameters—0.6 and 2.5 nm, respectively. Additionally, Lys- and Cys-CQDs, with high absolute zeta potential values, formed stable aqueous colloids in a broad range of pH (2, 7, and 12). The results constitute important premises for water-based applications of CQDs, such as bioimaging or photocatalysis.

https://pubs.acs.org/doi/pdf/10.1021/acsomega.2c04751

Carbon Quantum Dots from Amino Acids Revisited: Survey of Renewable Precursors toward High Quantum-Yield Blue and Green Fluorescence

Plant protein isolation by mild wet processing methods that are free of alkali/acid and thermal treatments were investigated in order to address the fast growing consumer demand for clean-label ingredients. The impact of different mild wet fractionation conditions was established in terms of yield, purity and recovery of faba bean protein concentrates/isolates (PCs/PIs) from both Snowbird (low tannin, LT) and Athena (high tannin, HT) cultivars. Although salt-soluble globulins (74 to 75%) were the primary proteins found in faba beans, PIs resulting from dialysis (LT: 93.2 ± 0.1% and HT: 96.4 ± 0.3%) or micellization (LT: 99.1 ± 0.1% and HT: 98.7 ± 0.2%) following water extraction at 35 °C (W35) at a solvent/feed (S/F) ratio of 2 had higher protein contents than PCs from aqueous NaCl extraction followed by dialysis (LT: 79.1 ± 0.1% and HT: 81.6 ± 0.5%) or alkali extraction followed by acid precipitation (LT: 87.1 ± 1.4% and HT: 86.3 ± 0.2%). These differences in protein extractability of water- and salt-based methods could be attributed to the high levels of endogenously present minerals. Although methionine and cysteine were limiting amino acids, the W35 methods resulted in overall higher amino acid content and in high-quality PIs compared to the rest due to the presence of albumins as confirmed by SDS-PAGE. The W35-PIs were low in raffinose family oligosaccharides, tannins and trypsin inhibitory activity and can be considered chemical-free alternatives to alkali extracted-acid precipitated PCs. 

Isolation of clean label faba bean (Vicia faba L) proteins: A comparative study of mild fractionation methods against traditional technologies

Polymer micelles represent one of the most attractive drug delivery systems due to their design flexibility based on a variety of macromolecular synthetic methods. The environmentally safe chemistry in which the use or generation of hazardous materials is minimized has an increasing impact on polymer-based drug delivery nanosystems. In this work, a solvent-free green synthetic procedure was applied for the preparation of an amphiphilic diblock copolymer consisting of biodegradable hydrophobic poly(acetylene-functional carbonate) and biocompatible hydrophilic polyethylene glycol (PEG) blocks. The cyclic functional carbonate monomer 5-methyl-5-propargyloxycarbonyl-1,3-dioxane-2-one (MPC) was polymerized in bulk using methoxy PEG-5K as a macroinitiator by applying the metal-free organocatalyzed controlled ring-opening polymerization at a relatively low temperature of 60 °C. The functional amphiphilic block copolymer self-associated in aqueous media into stable micelles with an average diameter of 44 nm. The copolymer micelles were physico-chemically characterized and loaded with the plant-derived anticancer drug curcumin. Preliminary in vitro evaluations indicate that the functional copolymer micelles are non-toxic and promising candidates for further investigation as nanocarriers for biomedical applications. 

/pdf/green-synthesis-and-the-evaluation-of-a-functional-2vdbr7jm.pdf

Green Synthesis and the Evaluation of a Functional Amphiphilic Block Copolymer as a Micellar Curcumin Delivery System

Natural amino acids and their derivatives are excellent building blocks of polymers for various biomedical applications owing to the non-toxicity, biocompatibility, and ease of multifunctionalization. In the present review, we summarized the common approaches to designing and constructing functional polymeric micelles based on basic amino acids including lysine, histidine, and arginine and highlighted their applications as drug carriers for cancer therapy. Different polypeptide architectures including linear polypeptides and dendrimers were developed for efficient drug loading and delivery. Besides, polylysine- and polyhistidine-based micelles could enable pH-responsive drug release, and polyarginine can realize enhanced membrane penetration and gas therapy by generating metabolites of nitric oxide (NO). It is worth mentioning that according to the structural or functional characteristics of basic amino acids and their derivatives, key points for designing functional micelles with excellent drug delivery efficiency are importantly elaborated in order to pave the way for exploring micelles based on basic amino acids.

/pdf/micelles-based-on-lysine-histidine-or-arginine-designing-2a06rxrklu.pdf

Li Xie

Papers

Micelles Based on Lysine, Histidine, or Arginine: Designing Structures for Enhanced Drug Delivery.