Quercetin (Que) and its derivatives are naturally occurring phytochemicals with promising bioactive effects. The antidiabetic, anti-inflammatory, antioxidant, antimicrobial, anti-Alzheimer's, antiarthritic, cardiovascular, and wound-healing effects of Que have been extensively investigated, as well as its anticancer activity against different cancer cell lines has been recently reported. Que and its derivatives are found predominantly in the Western diet, and people might benefit from their protective effect just by taking them via diets or as a food supplement. Bioavailability-related drug-delivery systems of Que have also been markedly exploited, and Que nanoparticles appear as a promising platform to enhance their bioavailability. The present review aims to provide a brief overview of the therapeutic effects, new insights, and upcoming perspectives of Que.

Therapeutic Potential of Quercetin: New Insights and Perspectives for Human Health.

Multifunctionalization of carbon nanotubules is easily achieved by attaching functional molecules that provide specific advantages for microscopic applications. We fabricated a double photodynamic therapy (PDT) and photohyperthermia (PHT) cancer phototherapy system that uses a single laser. Zinc phthalocyanine (ZnPc) was loaded onto single-wall carbon nanohorns with holes opened (SWNHox), and the protein bovine serum albumin (BSA) was attached to the carboxyl groups of SWNHox. In this system, ZnPc was the PDT agent, SWNHox was the PHT agent, and BSA enhanced biocompatibility. The double phototherapy effect was confirmed in vitro and in vivo. When ZnPc-SWNHox-BSA was injected into tumors that were subcutaneously transplanted into mice, the tumors almost disappeared upon 670-nm laser irradiation. In contrast, the tumors continued to grow when only ZnPc or SWNHox-BSA was injected. We conclude that carbon nanotubules may be a valuable new tool for use in cancer phototherapy.

Fabrication of ZnPc/Protein Nanohorns for Double Photodynamic and Hyperthermic Cancer Phototherapy

Drug resistance, including adriamycin (ADR)-based therapeutic resistance, is a crucial cause of chemotherapy failure in breast cancer treatment. Acquired chemoresistance has been identified to be closely associated with the overexpression of P-glycoprotein (P-gp/ABCB1). Long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) can be involved in carcinogenesis; however, its roles in ABCB1-mediated ADR resistance are poorly understood. In this study, we identified a panel of differentially expressed lncRNAs, mRNAs, and microRNAs (miRNAs) in MCF-7 and MCF-7/ADR cell lines through RNA sequencing (RNA-seq) technologies. GAS5 level was downregulated whereas ABCB1 level was upregulated in the resistant breast cancer tissues and cells. Overexpression of GAS5 significantly enhanced the ADR sensitivity and apoptosis, and it inhibited the efflux function and expression of ABCB1 in vitro, while knockdown of GAS5 had the opposite effects. Further mechanism-related investigations indicated that GAS5 acted as an endogenous "sponge" by competing for miR-221-3p binding to regulate its target dickkopf 2 (DKK2), and then it inhibited the activation of the Wnt/β-catenin pathway. Functionally, GAS5 enhanced the anti-tumor effect of ADR in vivo. Collectively, our findings reveal that GAS5 exerted regulatory function in ADR resistance possibly through the miR-221-3p/DKK2 axis, providing a novel approach to develop promising therapeutic strategy for overcoming chemoresistance in breast cancer patients.

The lncRNA-GAS5/miR-221-3p/DKK2 Axis Modulates ABCB1-Mediated Adriamycin Resistance of Breast Cancer via the Wnt/β-Catenin Signaling Pathway.

Angiogenesis is a process of generation of de-novo blood vessels from already existing vasculature. It has a crucial role in different physiological process including wound healing, embryonic development, and tumor growth. The methods by which therapeutic drugs inhibit tumor angiogenesis are termed as anti-angiogenesis cancer therapy. Developments of angiogenic inhibiting drugs have various limitations causing a barrier for successful treatment of cancer, where angiogenesis plays an important role. In this context, investigators developed novel strategies using nanotechnological approaches that have demonstrated inherent antiangiogenic properties or used for the delivery of antiangiogenic agents in a targeted manner. In this present article, we decisively highlight the recent developments of various nanoparticles (NPs) including liposomes, lipid NPs, protein NPs, polymer NPs, inorganic NPs, viral and bio-inspired NPs for potential application in antiangiogenic cancer therapy. Additionally, the clinical perspectives, challenges of nanomedicine, and future perspectives are briefly analyzed.

Recent Advancements of Nanomedicine towards Antiangiogenic Therapy in Cancer.

PEGylation of model drug carriers enhances phagocytosis by primary human neutrophils.

A targeted nanoplatform co-delivering chemotherapeutic and antiangiogenic drugs as a tool to reverse multidrug resistance in breast cancer.

Chemo-photothermal synergistic treatment has a high potential to complement traditional cancer therapy and amplify its outcome. Precision in the delivery of these therapeutic agents to tumor cells has been indicated as being key to maximizing their therapeutic effects. Method: We developed a bio-orthogonal copper-free click-targeting nanocomposite system (DLQ/DZ) that markedly improved specific co-delivery of the chemotherapeutic agent doxorubicin and the photosensitizer zinc phthalocyanine to breast cancer cells via a two-step mechanism. In the first step, an azide-modified sugar (tetraacetylated N-azidoacetyl-D-mannosamine, Ac4ManNAz) was injected intratumorally for glycoengineering of the tumor cell surface. Subsequently, DLQ/DZ was administered to achieve tumor enrichment via bio-orthogonal copper-free click-targeting. Results: During the first step in our experiments, high density azide groups (3.23×107/cell) were successfully glycoengineered on the surface of tumor cells following Ac4ManNAz administration in vitro. Subsequently, the highly efficient bio-orthogonal click chemical reaction between receptor-like azide groups on tumor cells and DBCO on nanocomposites significantly enhanced the cellular uptake and tumor-specific distribution (4.6x increase) of the nanocomposites in vivo. Importantly, Ac4ManNAz+DLQ/DZ treatment augmented the anti-cancer effect of combined chemotherapy and PTT (96.1% inhibition rate), nearly ablating the tumor. Conclusions: This bio-orthogonal click-targeting combination strategy may provide a promising treatment approach for surficial breast cancers.

Jianan Qiao

Papers

A targeted nanoplatform co-delivering chemotherapeutic and antiangiogenic drugs as a tool to reverse multidrug resistance in breast cancer.

Bio-orthogonal click-targeting nanocomposites for chemo-photothermal synergistic therapy in breast cancer.

Reinforcing vascular normalization therapy with a bi-directional nano-system to achieve therapeutic-friendly tumor microenvironment.