Polymer‐Based Drug‐Free Therapeutics for Anticancer, Anti‐Inflammatory, and Antibacterial Treatment

Abstract

This paper summarizes the area of biomedicinal polymers, which serve as nanomedicines even though they do not contain any anticancer or antiinflammatory drugs. These polymer nanomedicines with unique design are in the literature highlighted as a novel class of therapeutics called “drug‐free macromolecular therapeutics.” Their therapeutic efficacy is based on the tailored multiple presentations of biologically active vectors, i.e., peptides, oligopeptides, or oligosaccharides. Thus, they enable, for example, to directly induce the apoptosis of malignant cells by the crosslinking of surface slowly internalizing receptors, or to deplete the efficacy of tumor‐associated proteins. The precise biorecognition of natural binding motifs by multiple vectors on the polymer construct remains the crucial part in the designing of these drug‐free nanomedicines. Here, the rationales, designs, synthetic approaches, and therapeutic potential of drug‐free macromolecular therapeutics consisting of various active vectors are described in detail. Recent developments and achievements for namely B‐cell lymphoma treatment, Gal‐3‐positive tumors, inflammative liver injury, and bacterial treatment are reviewed and highlighted. Finally, a possible future prospect within this highly exciting new field of nanomedicine research is presented.

Endothelial Cell Adhesion Molecules- (un)Attainable Targets for Nanomedicines

“…Indeed, several of these “drug-free” CAM-targeted NMs have proven their therapeutic potential in pre-clinical research ( 147 , 151 , 152 ). sLe X - or other glycomimetic ligand-bearing polymer treatment reduces neutrophil and/or macrophage infiltration in rodent models of inflammation, such as peritoneal inflammation ( 136 , 139 ), liver injury ( 140 ) and dermatitis ( 138 ).…”

Intracellular Self-Assembly of Peptides to Induce Apoptosis against Drug-Resistant Melanoma

“…Meanwhile, malignant melanoma exhibits a high prevalence of somatic mutations with general phenotypic characteristics of unlimited proliferation, high metastatic capacity, and excess melanin production by tyrosinase-catalyzed overoxidation. ,− Despite the profound research on its pathogenesis, there are still no effective treatment options against advanced melanoma. − Especially, the eradication of malignant melanoma in clinic is difficult due to high probability of metastasis and recurrence after traditional surgery and chemotherapy, which could be ascribed to long-term treatment-induced tolerance. − For example, although cisplatin provides satisfactory melanoma inhibition when first applied during treatment, it was likely to become inactivate against melanoma due to enhanced DNA repair and termination of DNA damage-mediated apoptotic pathways. − Different from nucleus-targeted chemotherapeutic drugs, the cytoskeleton is closely related to cell morphology, adhesion, metastasis, and even the fate of drug-resistant cells, which could also be targeted to treat malignant or resistant cancer as an alternative and effective approach. − Vinblastine as a typical microtubule-disruptive chemotherapy medication had been developed to treat broad-spectrum cancer with enhanced efficacy; however, severe side-effects such as extensive tissue damage, loss of white blood cells and blood platelets, and high blood pressure, restrict its clinical application. , Furthermore, chemotherapeutic drug-free treatment systems have attracted widespread attention due to their low systemic toxicity and high biocompatibility and their region-selective bioactivity for achieving precise treatment. − Therefore, it would be of great value to design and fabricate bioactive peptides for cytoskeletal interference therapies in the absence of chemotherapy for combating drug-resistant melanoma.…”

Glycopolymers Decorated with 3-O-Substituted Thiodigalactosides as Potent Multivalent Inhibitors of Galectin-3

“…HPMA copolymers are attractive for the design of nanomedicines suitable for in vivo use due to their water solubility and lack of toxicity and immunogenicity. Nanomedicines based on HPMA copolymers show favorable pharmacokinetics with prolonged circulation times and increased accumulation in solid tumors. , These nanomedicines can also be used as drug-free macromolecular therapeutics that exert a strong biological effect without the presence of cytotoxic drugs . A library of C-3/C-3′-substituted asymmetrical TDG glycomimetics were synthesized in two steps.…”

“…35,36 These nanomedicines can also be used as drug-free macromolecular therapeutics that exert a strong biological effect without the presence of cytotoxic drugs. 37 A library of C-3/C-3′-substituted asymmetrical TDG glycomimetics were synthesized in two steps. A multivalent presentation was achieved by conjugation to HPMA copolymers in various contents using copper-catalyzed alkyne-azide cycloaddition (CuAAC).…”