Nanoparticle design strategies for enhanced anticancer therapy by exploiting the tumour microenvironment

Abstract

Nanovehicles can efficiently carry and deliver anticancer agents to tumour sites. Compared with normal tissue, the tumour microenvironment has some unique properties, such as vascular abnormalities, hypoxia and acidic pH. There are many types of cells including tumour cells, macrophages, immune and fibroblasts cells, fed by defective blood vessels in the solid tumour. Exploiting the tumour microenvironment can benefit the design of nanoparticles for enhanced therapeutic effectiveness. In this review article, we summarized the recent progress in various nanoformulations for cancer therapy, with special emphasis on tumour microenvironment stimuli-responsive ones. Numerous tumour microenvironment modulation strategies with promising cancer therapeutic efficacy have also been highlighted. Future challenges and opportunities of design consideration are also discussed in details. We believe that these tumour microenvironment modulation strategies offer a good chance for the practical translation of nanoparticle formulas into clinic.

Engineering of inorganic nanoparticles as magnetic resonance imaging contrast agents

“…215 Future studies should focus on the specific interaction between MRI contrast performance of CAs and EPR effect to develop a clinically relevant and useful strategy for obtaining high-relaxivity NPs with an optimal balance between renal clearance and strong EPR effects over a suitable time scale ( e.g ., less than a few hours). 216 The hypoxic microenvironment in various tumors has received tremendous attention from researchers because it is closely related to the tumor’s aggressiveness and resistance to therapy, 217,218 and a number of NPs have been used to effectively eradicate hypoxic tumors in preclinical animal models. 219-222 Although in this review article we have discussed various strategies based on NPs for efficient MRI, there has been no literature report on hypoxia-responsive NPs as MRI CAs except on several chemical complexes for hypoxia-related MRI such as T 1 or T 2 CAs, 223 19 F-based probes, 224 and CEST probes.…”

Autonomous self-navigating drug-delivery vehicles: From Science Fiction to Reality

“…In the new paradigm of 'self-navigating tumor-targeting drugs', the vasculature-targeting peptides can serve as 'sensors' initiating extravasation and migration of targeted medicines from blood stream toward tumor microenvironment. Thus, there is a need in new peptide ligands that would target receptors of cancer cells and cells that belong to the tumor microenvironment [20]. Such peptides are also required in development of precise imaging and therapeutic nanodevices [69].…”

“…Development of autonomous self-navigating nanomedicines: change of the paradigm Clarifying the composition of the tumor microenvironment has allowed to discover biological hurdles undermining the potential of targeted drug-delivery nanomedicines in human patients [19,20]. To overcome these difficulties in nanomedicine migration, it was suggested to supply the tumor-targeting vehicles with multiple ligands targeted to different components of tumor microenvironment [24][25][26][27][28].…”

“…The paper introduces also landscape phages and their fusion proteins as potentially invaluable versatile tools -'explorers' for the study of tumor microenvironment, and universal construction material for development of the third generation of 'autonomous self-navigating' cancer nanomedicines [22]. Other required characteristics of modern nanomedical devices, mentioned above -"a means for destruction of biological barriers and tumor-surrounding threat cells", and "traceability for imaging of the nanovehicle location", are currently considered in the scope of one concept -'theranostics', and are developed and presented separately from this work [23].Development of autonomous self-navigating nanomedicines: change of the paradigm Clarifying the composition of the tumor microenvironment has allowed to discover biological hurdles undermining the potential of targeted drug-delivery nanomedicines in human patients [19,20]. To overcome these difficulties in nanomedicine migration, it was suggested to supply the tumor-targeting vehicles with multiple ligands targeted to different components of tumor microenvironment [24][25][26][27][28].…”

“…As was noted by Maeda, one of the authors of EPR-based targeting concept [14], "many experimental scientists and pharmacologists and nanotechnology engineers hold to the premise that solid tumors consist of uniform tissues, i.e., that tumors are homogeneous" [15]. Currently, it is commonly recognized that solid tumors are nonhomogeneous and represent a well-organized ensemble of tumor and stromal cells, such as fibroblasts, smooth muscle, endothelial, vascular and immune cells accommodated in a network of extracellular matrix and secreted extracellular molecules [18][19][20]. Proficient nanomedicines should run a long way though all these barriers to reach and attack the target tumor cells and further -to penetrate and bring the drug cargo to the target cellular compartment.…”