TY - JOUR
T1 - Self-assembling prodrug nanotherapeutics for synergistic tumor targeted drug delivery
AU - Wang, Zhiren
AU - Chen, Jiawei
AU - Little, Nicholas
AU - Lu, Jianqin
N1 - Funding Information:
This work was supported in part by a Startup Fund from the College of Pharmacy at The University of Arizona and two COVID-19 Rapid Turn-Around Seed Grants from the BIO5 Institute and the Technology and Research Initiative Fund (TRIF), and by NIH grants P30 ES006694 and R35 ES031575.
Publisher Copyright:
© 2020
PY - 2020/7/15
Y1 - 2020/7/15
N2 - Self-assembling prodrugs represents a robust and effective nanotherapeutic approach for delivering poorly soluble anticancer drugs. With numerous intrinsic advantages, self-assembling prodrugs possess the maximum drug loading capacity, controlled drug release kinetics, prolonged blood circulation, and preferential tumor accumulation based on the enhanced permeability and retention (EPR) effect. These prodrug conjugates allow for efficient self-assembly into nanodrugs with the potential of encapsulating other therapeutic agents that have different molecular targets, enabling simultaneous temporal-spatial release of drugs for synergistic antitumor efficacy with reduced systemic side effects. The aim of this review is to summarize the recent progress of self-assembling prodrug cancer nanotherapeutics that are made through conjugating therapeutically active agents to Polyethylene glycol, Vitamin E, or drugs with different physicochemical properties via rational design, for synergistic tumor targeted drug delivery. Statement of Significance: All current FDA-approved nanomedicines use inert biomaterials as drug delivery carriers. These biomaterials lack any therapeutic potential, contributing not only to the cost, but may also elicit severe unfavorable adverse effects. Despite the reduction in toxicity associated with the payload, these nanotherapeutics have been met with limited clinical success, likely due to the monotherapy regimen. The self-assembling prodrug (SAP) has been emerging as a powerful platform for enhancing efficacy through co-delivering other therapeutic modalities with distinct molecular targets. Herein, we opportunely present a comprehensive review article summarizing three unique approaches of making SAP for synergistic drug delivery: pegylation, vitamin E-derivatization, and drug-drug conjugation. These SAPs may inevitably pave the way for developing more efficacious, clinically translatable, combination cancer nanotherapies.
AB - Self-assembling prodrugs represents a robust and effective nanotherapeutic approach for delivering poorly soluble anticancer drugs. With numerous intrinsic advantages, self-assembling prodrugs possess the maximum drug loading capacity, controlled drug release kinetics, prolonged blood circulation, and preferential tumor accumulation based on the enhanced permeability and retention (EPR) effect. These prodrug conjugates allow for efficient self-assembly into nanodrugs with the potential of encapsulating other therapeutic agents that have different molecular targets, enabling simultaneous temporal-spatial release of drugs for synergistic antitumor efficacy with reduced systemic side effects. The aim of this review is to summarize the recent progress of self-assembling prodrug cancer nanotherapeutics that are made through conjugating therapeutically active agents to Polyethylene glycol, Vitamin E, or drugs with different physicochemical properties via rational design, for synergistic tumor targeted drug delivery. Statement of Significance: All current FDA-approved nanomedicines use inert biomaterials as drug delivery carriers. These biomaterials lack any therapeutic potential, contributing not only to the cost, but may also elicit severe unfavorable adverse effects. Despite the reduction in toxicity associated with the payload, these nanotherapeutics have been met with limited clinical success, likely due to the monotherapy regimen. The self-assembling prodrug (SAP) has been emerging as a powerful platform for enhancing efficacy through co-delivering other therapeutic modalities with distinct molecular targets. Herein, we opportunely present a comprehensive review article summarizing three unique approaches of making SAP for synergistic drug delivery: pegylation, vitamin E-derivatization, and drug-drug conjugation. These SAPs may inevitably pave the way for developing more efficacious, clinically translatable, combination cancer nanotherapies.
KW - Enhanced Cancer Therapy
KW - Nanotherapeutics
KW - Self-assembling prodrug
KW - Synergistic drug delivery
UR - http://www.scopus.com/inward/record.url?scp=85086372000&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086372000&partnerID=8YFLogxK
U2 - 10.1016/j.actbio.2020.05.026
DO - 10.1016/j.actbio.2020.05.026
M3 - Review article
C2 - 32454086
AN - SCOPUS:85086372000
SN - 1742-7061
VL - 111
SP - 20
EP - 28
JO - Acta Biomaterialia
JF - Acta Biomaterialia
ER -