Rational Design of Cancer Nanomedicine: Nanoproperty Integration and Synchronization

Abstract

Current cancer nanomedicines can only mitigate adverse effects but fail to enhance therapeutic efficacies of anticancer drugs. Rational design of next-generation cancer nanomedicines should aim to enhance their therapeutic efficacies. Taking this into account, this review first analyzes the typical cancer-drug-delivery process of an intravenously administered nanomedicine and concludes that the delivery involves a five-step CAPIR cascade and that high efficiency at every step is critical to guarantee high overall therapeutic efficiency. Further analysis shows that the nanoproperties needed in each step for a nanomedicine to maximize its efficiency are different and even opposing in different steps, particularly what the authors call the PEG, surface-charge, size and stability dilemmas. To resolve those dilemmas in order to integrate all needed nanoproperties into one nanomedicine, stability, surface and size nanoproperty transitions (3S transitions for short) are proposed and the reported strategies to realize these transitions are comprehensively summarized. Examples of nanomedicines capable of the 3S transitions are discussed, as are future research directions to design high-performance cancer nanomedicines and their clinical translations.

Immunomodulatory Nanosystems

“…[130,131] These clinical researches confirmed their great therapeutic potential as antitumor agents. [56,126,[132][133][134] In this section, we overview the recent developments in the use of engineered nanoparticles to enhance cancer immunotherapy. [67] To achieve precise and controlled drug delivery, smart nanoparticles with more complex structures and specific drug release properties are also being produced according to the hallmarks of TME, such as weak acidic pH (6.5-6.8), high level of glutathione and hydrogen peroxide (H 2 O 2 ), and disorder of proteinases production, such as matrix metalloproteinase-2 (MMP-2).…”

Copper as the Target for Anticancer Nanomedicine

“…[125,126] Therefore, many copper-based nanomedicines have been developed, including copper-depleting nanomedicines and copper nanotoxins. Furthermore, the off-target effects of these agents on healthy cells cause side effects.…”

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

“…Although, clinical results demonstrated the enhanced tumor accumulation with reduced side effects as compared to the free drugs, the higher drug concentration achieved was unable to provide better therapeutic efficacy. [19,120] Furthermore, polymeric micelles (NK105) [199] and nanoparticles (CRLX101) [214] have also shown disappointing clinical outcomes pressing the importance of reconsidering the design strategies of nanomedicines that will have significant impact on improving therapeutic efficacy and ultimately long term overall survival rates of patients.…”

“…[14][15][16][17] In this direction, an array of nanomedicines has been synthesized, engineered with different physiochemical properties, such as size, shape and surface chemistry, and formulated with a large variety of anti-cancer therapeutics, including surface modifications with, e.g., polyethylene glycol (PEG) or other coatings, in order to extend the circulation time of the nanomedicines in bloodstream. [18][19][20] Various targeting moieties, such as antibodies, peptides, sugars and proteins, have also been attached to nanomedicines in different ways to further facilitate their selective accumulation within the tumors. [21,22] Furthermore, more complex and advanced nanomedicines designs equipped with multiple functions, such as combined therapeutics, imaging, diagnostic moieties with programmed release, have also been developed to improve the therapy of cancer.…”