Innovative Design of Targeted Nanoparticles: Polymer–Drug Conjugates for Enhanced Cancer Therapy

Abstract

Polymer–drug conjugates (PDCs) have shown great promise in enhancing the efficacy and safety of cancer therapy. These conjugates combine the advantageous properties of both polymers and drugs, leading to improved pharmacokinetics, controlled drug release, and targeted delivery to tumor tissues. This review provides a comprehensive overview of recent developments in PDCs for cancer therapy. First, various types of polymers used in these conjugates are discussed, including synthetic polymers, such as poly(↋-caprolactone) (PCL), D-α-tocopheryl polyethylene glycol (TPGS), and polyethylene glycol (PEG), as well as natural polymers such as hyaluronic acid (HA). The choice of polymer is crucial to achieving desired properties, such as stability, biocompatibility, and controlled drug release. Subsequently, the strategies for conjugating drugs to polymers are explored, including covalent bonding, which enables a stable linkage between the polymer and the drug, ensuring controlled release and minimizing premature drug release. The use of polymers can extend the circulation time of the drug, facilitating enhanced accumulation within tumor tissues through the enhanced permeability and retention (EPR) effect. This, in turn, results in improved drug efficacy and reduced systemic toxicity. Moreover, the importance of tumor-targeting ligands in PDCs is highlighted. Various ligands, such as antibodies, peptides, aptamers, folic acid, herceptin, and HA, can be incorporated into conjugates to selectively deliver the drug to tumor cells, reducing off-target effects and improving therapeutic outcomes. In conclusion, PDCs have emerged as a versatile and effective approach to cancer therapy. Their ability to combine the advantages of polymers and drugs offers enhanced drug delivery, controlled release, and targeted treatment, thereby improving the overall efficacy and safety of cancer therapies. Further research and development in this field has great potential to advance personalized cancer treatment options.

STING-Activating Polymer-Drug Conjugates for Cancer Immunotherapy

“…40 Conjugation of drugs to hydrophilic polymeric carriers can increase their circulation time and promote accumulation at tumor sites in a molecular weight-dependent manner. 41 We therefore evaluated the pharmacokinetics and biodistribution of Cy5-labeled SAPCon. To evaluate pharmacokinetics, healthy mice were intravenously injected with either SAPCon[25kDa] or SAPCon[100kDa] at a diABZI dose of approximately 0.012 μmol/mouse, and blood was sampled over 24 h for spectrofluorometric quantification of polymer concentration as a function of time.…”

“…34 Conjugation of drugs to hydrophilic polymeric carriers can increase their circulation time and promote accumulation at tumor sites in a molecular weight-dependent manner. 35 We therefore evaluated the pharmacokinetics and biodistribution of Cy5-labeled SAPCon. 4A).…”

Polymer–Drug Conjugates Codeliver a Temozolomide Intermediate and Nitric Oxide for Enhanced Chemotherapy against Glioblastoma Multiforme

“…1−3 Polymer−drug conjugates (PDCs), covalently tethering prodrugs to a polymer instead of encapsulation or adsorption, protect prodrugs from leakage and invalidation in circulation, escort them for cellular uptake and release drugs in the target sites. 4,5 Moreover, the structures of prodrugs could be diverse in the forms of organic molecules, inorganic clusters, or metal−organic complexes. 6−8 Prodrugs can be precisely installed as a part of the monomer before polymerization or the side chain after polymerization by stimulus cleavable bonds.…”

“…6−8 Prodrugs can be precisely installed as a part of the monomer before polymerization or the side chain after polymerization by stimulus cleavable bonds. 5 Environmentally sensitive polymeric prodrugs responsive to reactive oxygen species (ROS), glutathione (GSH), singlet oxygen ( 1 O 2 ), light, ultrasonic, etc., have been widely used for controlled prodrug release. 9−12 To make the most use of PDC capacity, it is feasible to further improve tumor treatment performance with two or more types of responsive prodrugs together for combination medications.…”

“…Polymer-based drug delivery systems have attracted massive attention in cancer chemotherapy, owing to the tunable backbones and flexible functionalization of side chains achieving their superior biocompatibility, water dispersibility, targeting capability, biodegradability, etc. − Polymer–drug conjugates (PDCs), covalently tethering prodrugs to a polymer instead of encapsulation or adsorption, protect prodrugs from leakage and invalidation in circulation, escort them for cellular uptake and release drugs in the target sites. , Moreover, the structures of prodrugs could be diverse in the forms of organic molecules, inorganic clusters, or metal–organic complexes. − Prodrugs can be precisely installed as a part of the monomer before polymerization or the side chain after polymerization by stimulus cleavable bonds . Environmentally sensitive polymeric prodrugs responsive to reactive oxygen species (ROS), glutathione (GSH), singlet oxygen ( 1 O 2 ), light, ultrasonic, etc., have been widely used for controlled prodrug release. − To make the most use of PDC capacity, it is feasible to further improve tumor treatment performance with two or more types of responsive prodrugs together for combination medications.…”