Small‐Molecule Prodrug Nanoassemblies: An Emerging Nanoplatform for Anticancer Drug Delivery

Abstract

The antitumor efficiency and clinical translation of traditional nanomedicines is mainly restricted by low drug loading, complex preparation technology, and potential toxicity caused by the overused carrier materials. In recent decades, small‐molecule prodrug nanoassemblies (SMP‐NAs), which are formed by the self‐assembly of prodrugs themselves, have been widely investigated with distinct advantages of ultrahigh drug‐loading and negligible excipients‐trigged adverse reaction. Benefited from the simple preparation process, SMP‐NAs are widely used for chemotherapy, phototherapy, immunotherapy, and tumor diagnosis. In addition, combination therapy based on the accurate co‐delivery behavior of SMP‐NAs can effectively address the challenges of tumor heterogeneity and multidrug resistance. Recent trends in SMP‐NAs are outlined, and the corresponding self‐assembly mechanisms are discussed in detail. Besides, the smart stimuli‐responsive SMP‐NAs and the combination therapy based on SMP‐NAs are summarized, with special emphasis on the structure–function relationships. Finally, the outlooks and potential challenges of SMP‐NAs in cancer therapy are highlighted.

Lipid based nanoparticles as a novel treatment modality for hepatocellular carcinoma: a comprehensive review on targeting and recent advances

“…In order to increase the treatment efficacy, prodrug nanoassemblies have been developed. Prodrug nanoassemblies utilize both prodrug and nanoparticles through modifying the active constituent structure with another moiety rendering the structure amphiphilic [ 137 ]. Zuo et al prepared 1-O-octodecyl-2-conjugated linoleoyl-sn-glycero-3-phosphatidyl gemcitabine.…”

Research progress on self-assembled nanodrug delivery systems

“…More importantly, a self-assembled nanodrug delivery system is easy to synthesize through only a one-step nanoprecipitation method. 16 In recent years, self-assembly technology has become a hotspot in biomedical research. Generally, self-assembled nanodrug delivery systems include amphiphilic block copolymer-based self-assembled nanodrug delivery systems, carrier-free self-assembled nanodrug delivery systems, peptide self-assembled drug delivery systems, metal–polyphenol assembly, and self-assembled drug delivery systems based on natural small molecules.…”

Binary dimeric prodrug nanoparticles for self-boosted drug release and synergistic chemo-photodynamic therapy

“…A prodrug is an inactive preparation and can easily be converted to its bioactive form in vivo . 19 Idealized prodrugs can be activated by a specific stimulus in the tumor microenvironment, such as acidity, high glutathione or reactive oxygen species (ROS), or specific enzymes. 20 As a result, the rational design of prodrugs in combination with nanotechnology can significantly improve the delivery efficiency and reduce undesirable drug leakage.…”