Glycosylated Nanoparticles for Cancer-Targeted Drug Delivery

Abstract

Nanoparticles (NPs) are novel platforms that can carry both cancer-targeting molecules and drugs to avoid severe side effects due to nonspecific drug delivery in standard chemotherapy treatments. Cancer cells are characterized by abnormal membranes, metabolic changes, the presence of lectin receptors, glucose transporters (GLUT) overexpression, and glycosylation of immune receptors of programmed death on cell surfaces. These characteristics have led to the development of several strategies for cancer therapy, including a large number of carbohydrate-modified NPs, which have become desirable for use in cell-selective drug delivery systems because they increase nanoparticle-cell interactions and uptake of carried drugs. Currently, the potential of NP glycosylation to enhance the safety and efficacy of carried therapeutic antitumor agents has been widely acknowledged, and much information is accumulating in this field. This review seeks to highlight recent advances in NP stabilization, toxicity reduction, and pharmacokinetic improvement and the promising potential of NP glycosylation from the perspective of molecular mechanisms described for drug delivery systems for cancer therapy. From preclinical proof-of-concept to demonstration of therapeutic value in the clinic, the challenges and opportunities presented by glycosylated NPs, with a focus on their applicability in the development of nanodrugs, are discussed in this review.

PSMA-Targeting Imaging and Theranostic Agents—Current Status and Future Perspective

“…Glycosylation, a common method used to modulate the targeting drug delivery [83,84] has been used to optimize the lipophilicity, in vivo kinetics, and tumor-targeting properties of 18 F-labeled PSMA-targeting agents. A report with two 18 F-fluoroglycosylated ureabased PSMA agents, 2-[ 18 F]FGlc-PSMA and 6-[ 18 F]FGlc-PSMA (Figure 4), demonstrated that incorporation of an 18 F-labeled glycosyl moiety increases the hydrophilicity thus improving the tumor-to-kidney ratio [79].…”

Strategies for Glycoengineering Therapeutic Proteins

“…Also in the future, additional forms of glycosylation including O-, C-, or S- will provide additional avenues to improve therapeutic proteins. Moreover, the glycoengineering “toolkit” described in Section 5 provides methodology to improve additional biological therapeutics including antimicrobial peptides (AMPs); glycosylated nanoparticles, liposomes, and exosomes for drug delivery and bioimaging; and glycodendrimers ( Jain et al, 2012 ; Grimsey et al, 2020 ; Torres-Pérez et al, 2020 ). The safety of these biopharmaceuticals, including toxicity and immunogenicity, are impacted by glycosylation and, similar to antibodies, their glycoprofiles are critical quality control attributes during biomanufacturing ( Mastrangeli et al, 2019 ).…”

Glycans as Targets for Drug Delivery in Cancer

“…Over the last decade, several efforts have been made to integrate nanotechnology and carbohydrate field for the targeted and controlled delivery of cancer therapeutic agents. Several studies have demonstrated the importance of using glycosylated NPs for therapeutic purposes (reviewed in [ 95 , 100 ]).…”