Tumor Abnormality-Oriented Nanomedicine Design

Abstract

Anticancer nanomedicines have been proven effective in mitigating the side effects of chemotherapeutic drugs. However, challenges remain in augmenting their therapeutic efficacy. Nanomedicines responsive to the pathological abnormalities in the tumor microenvironment (TME) are expected to overcome the biological limitations of conventional nanomedicines, enhance the therapeutic efficacies, and further reduce the side effects. This Review aims to quantitate the various pathological abnormalities in the TME, which may serve as unique endogenous stimuli for the design of stimuli-responsive nanomedicines, and to provide a broad and objective perspective on the current understanding of stimuli-responsive nanomedicines for cancer treatment. We dissect the typical transport process and barriers of cancer drug delivery, highlight the key design principles of stimuli-responsive nanomedicines designed to tackle the series of barriers in the typical drug delivery process, and discuss the “all-into-one” and “one-for-all” strategies for integrating the needed properties for nanomedicines. Ultimately, we provide insight into the challenges and future perspectives toward the clinical translation of stimuli-responsive nanomedicines.

Nanomedomics

“…Nanomedicines need to go through a five-step cascade process before functioning, blood circulation, accumulation to the tumor site, intratumor penetration, endocytosis by the cells, and intracellular release of the drug. 116 Each step is a barrier, if we use nanomedomics to make a clear study of the key influencing factors of each barrier, and design nanomedicines to specifically target these key factors, we can design highly effective targeting nanomedicines. For example, in the blood circulation process, protein crowns are considered to be an important factor affecting the clearance of nanoparticles.…”

Tumor Mechanics Meets Nanomedicine Mechanical Properties

“…Nanomedicines for cancer therapy have gained tremendous attention and have been widely developed during the past few decades. , After loading by nanoparticles, the pharmacokinetics and biodistribution of traditional small molecule drugs were observably improved, because nanoparticles endow efficient tumor targeting ability and reduced side effects to normal tissues, via the enhanced permeability and retention (EPR) effect. , More importantly, many nanomedicines have been commercialized and applied to clinical cancer therapy, such as Doxil and Abraxane . It is a complicated progress for tumor targeting delivery of nanomedicine, usually containing five critical processes which are long circulation, tumor accumulation, deep penetration, cellular internalization, and drug release. , To achieve the optimal antitumor efficacy and minimal side effects, the physicochemical properties of nanomedicines have been investigated and optimized including the size, surface charge, shape, components, and so on .…”

Self-supplying Cu2+ and H2O2 synergistically enhancing disulfiram-mediated melanoma chemotherapy

“…28 Furthermore, most nanoparticles are distributed in normal tissues during circulation, which can result in much more complicated therapeutic outcomes and severe side effects. 30,31…”

“…28 Furthermore, most nanoparticles are distributed in normal tissues during circulation, which can result in much more complicated therapeutic outcomes and severe side effects. 30,31 Herein, to improve the utilization of DSF to treat melanoma, we proposed polyvinyl pyrrolidone (PVP)-coated CuO 2 nanodot (CPND)-mediated H 2 O 2 /Cu 2+ self-supplying enhanced DSFmediated chemotherapy as a smart therapeutic strategy for synergistic treatment of melanoma (Scheme 1). Taking DSF orally, 32 it can be decomposed to DTC in the digestive tract, which is then delivered to the tumor via circulation.…”