Publications by authors named "Qianzhu Xu"

Article Synopsis
  • The blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) limit the effectiveness of chemotherapy for treating gliomas, necessitating a drug delivery system that can target glioma cells specifically while reducing overall toxicity.
  • Researchers identified high expression of glucose-regulated protein 78 (GRP78) and dopamine receptor D2 in glioma tissues, and synthesized a "Y"-shaped peptide to enhance drug affinity and targeting capability.
  • The developed peptide-drug conjugate (pHA-AOHX-VAP-DOX) effectively crossed the BBB and BBTB, targeted glioma cells, improved survival in animal models, and reduced the side effects of the chemotherapy drug doxorubicin (DOX
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Challenges for glioma treatment with nanomedicines include physio-anatomical barriers (the blood-brain barrier and blood-brain tumor barrier), low drug loading capacity, and limited circulation time. Here, a red blood cell membrane-coated docetaxel drug nanocrystal (pV-RBCm-NC(DTX)), modified with pHA-VAP (pV) for all-stage targeting of glioma, was designed. The NC(DTX) core exhibited a high drug loading capacity but low in vivo stability, and the RBCm coating significantly enhanced the stability and prolonged in vivo circulation.

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Brain metastasis is a common and serious complication of breast cancer, which is commonly associated with poor survival and prognosis. In particular, the treatment of brain metastasis from triple-negative breast cancer (BM-TNBC) has to face the distinct therapeutic challenges from tumor heterogeneity, circulating tumor cells (CTCs), blood-brain barrier (BBB) and blood-tumor barrier (BTB), which is in unmet clinical needs. Herein, combining with the advantages of synthetic and natural targeting moieties, we develop a "Y-shaped" peptide pVAP-decorated platelet-hybrid liposome drug delivery system to address the all-stage targeted drug delivery for the whole progression of BM-TNBC.

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Article Synopsis
  • There is growing evidence that the effectiveness of nanodrugs in fighting tumors is much better in mouse models than in actual human tumors, likely due to the different characteristics of tumor models used.
  • The study found that faster-growing tumors have lower vascular tight junctions, which increases the accumulation of nanodrugs, while orthotopic tumors have low transport activities, making it hard for nanodrugs to target these tumors effectively.
  • The researchers emphasize that the enhanced permeability and retention (EPR) effect varies significantly between different tumor models, suggesting that it may not be a one-size-fits-all approach for designing antitumor nanodrugs, and caution against overstating their effectiveness based on preclinical results.
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Thrombolytic agents have thus far yielded limited therapeutic benefits in the treatment of thrombotic disease due to their short half-life, low targeting ability, and association with serious adverse reactions, such as bleeding complications. Inspired by the natural roles of platelets during thrombus formation, we fabricated a platelet-based delivery system (NO@uPA/PLTs) comprising urokinase (uPA) and arginine (Arg) for targeted thrombolysis and inhibition of re-embolism. The anchoring of uPA to the platelet surface by lipid insertion increased the thrombotic targeting and circulation duration of uPA without disturbing platelet functions.

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Drug nanocrystals, which are comprised of active pharmaceutical ingredients and only a small amount of essential stabilizers, have the ability to improve the solubility, dissolution and bioavailability of poorly water-soluble drugs; in turn, drug nanocrystal technology can be utilized to develop novel formulations of chemotherapeutic drugs. Compared with passive targeting strategy, active tumor-targeted drug delivery, typically enabled by specific targeting ligands or molecules modified onto the surface of nanomedicines, circumvents the weak and heterogeneous enhanced permeability and retention (EPR) effect in human tumors and overcomes the disadvantages of nonspecific drug distribution, high administration dosage and undesired side effects, thereby contributing to improving the efficacy and safety of conventional nanomedicines for chemotherapy. Continuous efforts have been made in the development of active tumor-targeted drug nanocrystals delivery systems in recent years, most of which are encouraging and also enlightening for further investigation and clinical translation.

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Chemotherapy is still the mainstay treatment for metastatic triple-negative breast cancers (TNBC) currently in clinical practice. The unmet needs of chemotherapy for metastatic TNBC are mainly from the insufficient drug delivery and unavailable targeting strategy that thwart the whole progression of metastatic TNBC. The in vivo ligands-mediated active targeting efficiency is usually affected by protein corona.

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Article Synopsis
  • Glioblastoma (GBM) is a highly aggressive brain tumor associated with a poor prognosis and frequent recurrence, complicated by barriers that limit drug delivery to the tumor site.
  • * The study introduces a novel treatment approach utilizing a targeted liposome formulation (pV-Lip/cNC) that combines a D-peptide ligand (VAP) and p-hydroxybenzoic acid (pHA) to effectively cross the blood-brain barrier (BBB).
  • * In preclinical models, this treatment significantly improved drug accumulation in glioma cells and extended survival time in mice compared to single-ligand treatments, suggesting that pV-Lip/cNC could offer a promising strategy for treating all stages of glioma.
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Glioblastoma, the most common malignant tumor of the central nervous system, readily relapses after surgery. Based on the CD47-SIRPα axis, we designed and implanted a thermo-sensitive hydrogel loaded with a gene complex into the postoperative cavity to inhibit the immune escape of residual tumor cells after surgery. A novel non-viral vector, G5-BGG, was synthesized and formed into a gene complex with shRNA plasmid.

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