Multiple cues on the physiochemical, mesenchymal, and intracellular trafficking interactions with nanocarriers to maximize tumor target efficiency

Abstract

Over the past 60 years, numerous medical strategies have been employed to overcome neoplasms. In fact, with the exception of lung, bronchial, and pancreatic cancers, the 5-year survival rate of most cancers currently exceeds 70%. However, the quality of life of patients during chemotherapy remains unsatisfactory despite the increase in survival rate. The side effects of current chemotherapies stem from poor target efficiency at tumor sites due to the uncontrolled biodistribution of anticancer agents (ie, conventional or current approved nanodrugs). This review discusses the effective physiochemical factors for determining biodistribution of nanocarriers and, ultimately, increasing tumor-targeting probability by avoiding the reticuloendothelial system. Second, stem cell-conjugated nanotherapeutics was addressed to maximize the tumor searching ability and to inhibit tumor growth. Lastly, physicochemical material properties of anticancer nanodrugs were discussed for targeting cellular organelles with modulation of drug-release time. A better understanding of suggested topics will increase the tumor-targeting ability of anticancer drugs and, ultimately, promote the quality of life of cancer patients during chemotherapy.

<p>CD-340 functionalized doxorubicin-loaded nanoparticle induces apoptosis and reduces tumor volume along with drug-related cardiotoxicity in mice</p>

“…DOX-Ab-NP/DOX-NPs were internalized by endocytosis which might follow endosomal escape and delivered the encapsulated drug to the cytosol 45. Higher intracellular delivery of the nanoparticles usually reflects the efficacy of encapsulated DOX 46.…”

<p>Past, Present, and Future of Anticancer Nanomedicine</p>

“…Therefore, to maximize the targeted nanodrug delivery, it is essential to determine the optimal blood circulation time. 15 One strategy to adjust the optimal blood circulation time of nanodrugs is to control their polyethylene glycol (PEG)/polylactic acid (PLA) ratio by changing the molecular weight ratios of PEG and PLA. 111 , 112 …”

“…[92][93][94] Researchers believed that by carefully designing the unique physiochemical properties of nanodrugs, their anticancer efficacy could be enhanced. 15 Additionally, nanodrugs have the ability to evade cancer efflux pumps and optimize intracellular endosomal drug delivery, allowing nanodrugs to selectively destroy the cancer cell. [95][96][97] However, the greatest drawbacks of nanodrug delivery for the clinical application of nanodrugs are the toxicity and clearance issues.…”

“…However, nanotechnology research has shown that changes in nanoparticle (NP) shape, size, and material can influence their biodistribution and improve their cellular uptake efficiency. 15,[100][101][102][103][104] For example, gold and liposome NPs are preferentially localized in the liver and blood, respectively. [105][106][107] Additionally, nanospheres, nanorods, and single walled carbon nanotubes (swCNTs) show different biodistributions.…”

“…However, the use of these nanodrugs resulted in toxicity and was not sufficiently effective considering aroused side effects by use of nanoparticles. 15,16 Recently, great efforts have been made to develop a novel immunotherapeutic strategy that effectively directs immune cells to react against invasive cancer cells. [17][18][19] The immune system, which includes immune checkpoints, the tumor microenvironment, dendritic cells (DC), or macrophages, can be appropriately manipulated to create the desired anticancer effect.…”