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.
Rational design of next‐generation cancer nanomedicines should aim to enhance their therapeutic efficacies. The typical cancer‐drug delivery involves a five‐step CAPIR cascade and that high efficiency at every step is critical to guarantee high overall therapeutic efficiency. Stability, surface, and size nanoproperty transitions (3S transitions for short) are proposed, and the reported strategies to realize these transitions are comprehensively summarized.
This paper reviews recent developments in the preparation, surface functionalization, and applications of Fe3O4 magnetic nanoparticles. Especially, it includes preparation methods (such as ...electrodeposition, polyol methods, etc.), organic materials (such as polymers, small molecules, surfactants, biomolecules, etc.) or inorganic materials (such as silica, metals, and metal oxidation/sulfide, functionalized coating of carbon surface, graphene, etc.) and its applications (such as magnetic separation, protein fixation, magnetic catalyst, environmental treatment, medical research, etc.). In the end, some existing challenges and possible future trends in the field were discussed.
Display omitted
•Comprehensive summary of the main aspects of Fe3O4 magnetic nanoparticles related to their preparation and application.•Classification and intrinsic properties of Fe3O4 magnetic nanoparticles were studied.•Perspectives for the future developments of Fe3O4 magnetic nanoparticles were proposed.
Cancer drug delivery achieving high therapeutic efficacy and low side effects requires a nanocarrier to tightly retain the drug, efficiently reach the tumor, then quickly enter the tumor cells and ...release the drug. Furthermore, the nanocarrier intended for clinical applications should use materials safe as pharmaceutical excipients and its formulation (nanomedicine) should have good manufacture processes with scale-up ability. Thus, the challenge is to design safe, approvable, and easily scaled-up nanocarriers that simultaneously meet the two pairs of requirements of ‘drug retention in circulation versus intracellular release’ and ‘stealthy in circulation versus sticky (cell-binding) in tumor’ at the right places in order to deliver a cytosolic drug dose lethal to cancer cells with minimized side effects. Herein, we briefly review these elements aimed at promoting developments of translational nanocarriers.
Display omitted
Anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) antibodies are currently used in the clinic to interupt the PD-1/PD-L1 immune checkpoint, which reverses T cell ...dysfunction/exhaustion and shows success in treating cancer. Here, we report a histone demethylase inhibitor, 5-carboxy-8-hydroxyquinoline (IOX1), which inhibits tumour histone demethylase Jumonji domain-containing 1A (JMJD1A) and thus downregulates its downstream β-catenin and subsequent PD-L1, providing an antibody-independent paradigm interrupting the PD-1/PD-L1 checkpoint. Synergistically, IOX1 inhibits cancer cells' P-glycoproteins (P-gp) through the JMJD1A/β-catenin/P-gp pathway and greatly enhances doxorubicin (DOX)-induced immune-stimulatory immunogenic cell death. As a result, the IOX1 and DOX combination greatly promotes T cell infiltration and activity and significantly reduces tumour immunosuppressive factors. Their liposomal combination reduces the growth of various murine tumours, including subcutaneous, orthotopic, and lung metastasis tumours, and offers a long-term immunological memory function against tumour rechallenging. This work provides a small molecule-based potent cancer chemo-immunotherapy.
Polymer micelles are one of the most investigated nanocarriers for drug delivery; many have entered clinical trials and some are in clinic use, but their delivery systems have not yet shown the ...expected high therapeutic efficacy in clinics. Further understanding their in vivo behaviors, particularly how quickly and by what mechanism polymer micelles are cleared (i.e., via micelles or unimers) once injected, is key to solving this dilemma. Herein, we hope to answer these questions for the clinically relevant polyethylene glycol-block-poly(ε-caprolactone) (PEG-PCL) and PEG-block-poly(d,l-lactide) (PEG-PDLLA) micelles. A small fraction of the hydrophobic chain ends was conjugated with a pair of fluorescence resonance energy transfer (FRET) dyes, Cy5 and Cy5.5, and used to fabricate FRET micelles whose FRET efficiency was correlated to the percentage of polymer chains in the micelles, the micelle degree. In vitro, serum proteins induced PEG-PCL micelle dissociation to some extent; mouse serum or blood surprisingly did not induce micelle dissociation but once with shear applied by a microfluidic channel caused most PEG-PCL micelles dissociated. After intravenous administration in mice, the PEG-PCL or PEG-PDLLA micelles were quickly sequestered into the liver as unimers, and the micelle degree in the blood quickly decreased to about 20%. The FRET-imaging experiments showed that in blood vessels the micelles quickly dissociated into unimers, which were found associated with albumin in blood and in liver. Thus, it is concluded that, upon intravenous injection, the shear and the bloodborne proteins (particularly albumin) induced the most (∼80%) PEG-PCL and PEG-PDLLA micelles to quickly dissociate into unimers, which were sequestered by Kupffer cells, while intact micelles were difficult to clear. These micelles were able to penetrate tumors and were very stable with cell membranes, but dissociated gradually inside cells. These findings on in vivo micelle fate and the clearance mechanism are directional for the rational design of polymer micelles for improved therapeutics; particularly, improving micelle stability in blood is the prerequisite for surface functionalizations such as introducing targeting ligands.
Display omitted
Over the past three decades, the enhanced permeability and retention (EPR) effect has been considered the basis of tumor-targeted drug delivery. Various cancer nanomedicines, ...including macromolecular drugs, have been designed to utilize this mechanism for preferential extravasation and accumulation in solid tumors. However, such nanomedicines have not yet achieved convincing therapeutic benefits in clinics. Increasing evidence suggests that the EPR effect is over-represented in human tumors, especially in metastatic tumors. This review covers the evolution of the concept, the heterogeneity and limitation of the EPR effect in clinical realities, and prospects for alternative strategies independent of the EPR effect.
At present, BODIPY and its derivatives are a kind of multifunctional photosensitive organic dyes, because of their small Stokes shift, strong absorption, narrow absorption and emission, low ...photobleaching, high fluorescence quantum efficiency, polarity, and pH insensitive and stable chemical structure, thus, it can be used in various fields such as medical treatment, energy, environmental protection and so on. This article mainly describes the application of BODIPY and its derivatives in photodynamic therapy, elaborates on its synthesis method, the role of photodynamic therapy, and discusses the factors that affect the location and efficacy of BODIPY photodynamic therapy. For the analysis and summary of BODIPY and its derivatives, we hope that this review can point the way for researchers.
•Summarized the synthetic methods of BODIPY and its derivatives.•Summarizes the principle of BODIPY as photodynamic therapy.•Put forward some new ideas on the research of BODIPY as photodynamic therapy.
A cascade amplification release nanoparticle (CARN) is constructed by the coencapsulation of β‐lapachone and a reactive‐oxygen‐species (ROS)‐responsive doxorubicin (DOX) prodrug, BDOX, in polymeric ...nanoparticles. Releasing β‐lapachone first from the CARNs selectively increases the ROS level in cancer cells via NAD(P)H:quinone oxidoreductase‐1 (NQO1) catalysis, which induces the cascade amplification release of DOX and overcomes multidrug resistance (MDR) in cancer cells, producing a remarkably improved therapeutic efficacy against MDR tumors with minimal side effects.
A cascade amplification release nanoparticle is constructed by loading β‐lapachone and a reactive‐oxygen‐species‐responsive doxorubicin (DOX) prodrug in polymeric nanoparticles. The selective cascade amplification release of β‐lapachone and DOX in cancer cells remarkably increases the selectivity of chemotherapy and overcomes the multidrug resistance (MDR) in cancer cells, producing a remarkably enhanced therapeutic efficacy against MDR tumors with minimal side effects.
Gene therapy represents a promising cancer treatment featuring high efficacy and limited side effects, but it is stymied by a lack of safe and efficient gene-delivery vectors. Cationic polymers and ...lipid-based nonviral gene vectors have many advantages and have been extensively explored for cancer gene delivery, but their low gene-expression efficiencies relative to viral vectors limit their clinical translations. Great efforts have thus been devoted to developing new carrier materials and fabricating functional vectors aimed at improving gene expression, but the overall efficiencies are still more or less at the same level. This review analyzes the cancer gene-delivery cascade and the barriers, the needed nanoproperties and the current strategies for overcoming these barriers, and outlines PEGylation, surface-charge, size, and stability dilemmas in vector nanoproperties to efficiently accomplish the cancer gene-delivery cascade. Stability, surface, and size transitions (3S Transitions) are proposed to resolve those dilemmas and strategies to realize these transitions are comprehensively summarized. The review concludes with a discussion of the future research directions to design high-performance nonviral gene vectors.
Display omitted
The specific sizes that determine optimal nanoparticle tumor accumulation, penetration, and treatment remain inconclusive because many studies compared nanoparticles with multiple physicochemical ...variables (e.g., chemical structures, shapes, and other physical properties) in addition to the size. In this study, we synthesized amphiphilic block copolymers of 7-ethyl-10-hydroxylcamptothecin (SN38) prodrug and fabricated micelles with sizes ranging from 20 to 300 nm from a single copolymer. The as-prepared micelles had exactly the same chemical structures and similar physical properties except for size, which provided an ideal platform for a systematic investigation of the size effects in cancer drug delivery. We found that the micelle’s blood circulation time and tumor accumulation increased with the increase in their diameters, with optimal diameter range of 100 to 160 nm. However, the much higher tumor accumulation of the large micelles (100 nm) did not result in significantly improved therapeutic efficacy, because the large micelles had poorer tumor penetration than the small ones (30 nm). An optimal size that balances drug accumulation and penetration in tumors is critical for improving the therapeutic efficacy of nanoparticulate drugs.
PDF
