The rapid development of nanotechnology results in the emergence of nanomedicines, but the effective delivery of drugs to tumor sites remains a great challenge. Prodrug-based cancer nanomedicines thus emerged due to their unique advantages, including high drug load efficiency, reduced side effects, efficient targeting, and real-time controllability. A distinctive characteristic of prodrug-based nanomedicines is that they need to be activated by a stimulus or multi-stimulus to produce an anti-tumor effect. A better understanding of various responsive approaches could allow researchers to perceive the mechanism of prodrug-based nanomedicines effectively and further optimize their design strategy. In this review, we highlight the stimuli-responsive pathway of prodrug-based nanomedicines and their anticancer applications. Furthermore, various types of prodrug-based nanomedicines, recent progress and prospects of stimuli-responsive prodrug-based nanomedicines and patient data in the clinical application are also summarized. Additionally, the current development and future challenges of prodrug-based nanomedicines are discussed. We expect that this review will be valuable for readers to gain a deeper understanding of the structure and development of prodrug-based cancer nanomedicines to design rational and effective drugs for clinical use.
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http://dx.doi.org/10.1016/j.ebiom.2020.102821 | DOI Listing |
J Mater Chem B
December 2024
Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry & Molecular Engineering, East China University of Science & Technology, 130# Meilong Road, Shanghai 200237, China.
The on-demand delivery and release of chemotherapeutic drugs have attracted great attention, among which photoresponsive prodrug systems have shown specific advantages for effective cancer treatment due to their spatiotemporal control, non-invasive nature and easy operation. Unlike the traditional strategy of physical encapsulation of drugs in liposomes, we herein report a biomimetic and photoresponsive drug delivery system (DDS) based on a lipid prodrug liposomal formulation (LNC), which combines the features of the prodrug and nanomedicines, and can realize photocontrollable release of anticancer drugs. The lipid prodrug comprises three functional moieties: a single-arm phospholipid (Lyso PC), an -nitrobenzyl alcohol (NB) and chlorambucil (CBL).
View Article and Find Full Text PDFBiomed Pharmacother
November 2024
Department of Radiology, the General Hospital of Eastern Command of the Chinese People's Liberation Army (PLA), Nanjing 210012, China. Electronic address:
Leukemia remains a fatal disease for most affected patients, and a simple and effective therapeutic strategy is urgently needed. Targeted delivery chemo-drugs to leukemia cells shows promise, but the diverse subtypes of leukemia make single-ligand nanomedicine often ineffective. Herein, a dual-aptamer decorated, reduction-responsive dimeric prodrug-based nanoparticle (NP), termed SXP-NPs, was developed using the two leukemia-specific aptamers Sgc8c and XQ-2d, a reduction-responsive podophyllotoxin (POD) dimeric prodrug, and DSPE-PEG2000.
View Article and Find Full Text PDFAdv Healthc Mater
December 2024
Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, V5Z 3P2, Canada.
Many patients cannot tolerate low-dose weekly methotrexate (MTX) therapy for inflammatory arthritis treatment due to life-threatening toxicity. Although biologics offer a target-specific therapy, it raises the risk of serious infections and even cancer due to immune system suppression. We introduce an anti-inflammatory arthritis MTX ester prodrug using a long-circulating biocompatible polymeric macromolecule: folic acid (FA) functionalized hyperbranched polyglycerol (HPG).
View Article and Find Full Text PDFPharmaceutics
September 2024
Central Lab Changzhi Medical College, Changzhi Medical College, Changzhi 046000, China.
Using an endogenous carrier is the best method to address the biocompatibility of carriers in the drug delivery field. Herein, we prepared a glutathione-responsive paclitaxel prodrug micelle based on an endogenous molecule of L-glutathione oxidized (GSSG) for cancer therapy using one-pot synthesis. The carboxyl groups in L-glutathione oxidized were reacted with the hydroxyl group in paclitaxel (PTX) using the catalysts dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP).
View Article and Find Full Text PDFACS Appl Mater Interfaces
September 2024
Hebei Key Laboratory of Functional Polymers, School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300130, China.
Insufficient drug accumulation in tumors severely limits the antitumor efficiency of hyaluronic acid (HA) nanomedicine in solid tumors due to superficial penetration depth, low cell uptake, and nonspecific drug release. Hence, we constructed a dual NO prodrug (alkynyl-JSK) and doxorubicin prodrug (-DOX)-conjugated HA nanoparticle (HA-DOX-JSK NPs), which achieved cascade-boosted drug delivery efficiency based on a relay strategy of NO-mediated deep tumor penetration─HA target CD44 tumor cell uptake─tumor microenvironment (TME)-responsive drug release. The nanoparticle demonstrated sustained and locoregionally GSH/GST-triggered NO release and GSH/pH-responsive DOX release in the tumor.
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