Publications by authors named "Xiaoyou Wang"

16 Publications

  • Page 1 of 1

A Programmed Cell-Mimicking Nanoparticle Driven by Potato Alkaloid for Targeted Cancer Chemoimmunotherapy.

Adv Healthc Mater 2021 May 8:e2100311. Epub 2021 May 8.

Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China.

Membrane camouflaged-nanoparticles (CM-NPs) have been exploited to inherit desired functionalities from source cells. Despite those advantages, membrane cloak may play a "double-edged sword" role in tumor-targeting therapy, as the intact membrane coating may hinder function-exertion of loaded drugs after reaching predetermined site. Therefore, further optimization of CM-NPs is still needed to enhance their delivery efficiency. Herein, natural product, Solamargine (SM), a cholesterol-affiliative amphiphilic potato alkaloid is first applied as core component of "inner core," to design a cell-mimicking "core-shell" nanoparticle (RBC-SLip) with acid-responsive off-coating properties for tumor-targeted therapy. Owing to red blood cell membrane (RBCm)-derived outer coating, it circulates stably in physiological conditions. While it would undergo an off-coating morphological change in response to acid stimuli in tumor microenvironment (TME), afterwards, the resulting off-coating liposome (SLip) shows active tumor-targeting and endosomal escape abilities, thus contributing to superior antitumor efficacy. In addition, SM also possesses natural TME-modulating ability; therefore, RBC-SLip can synergize with the PD1/PD-L1 blockade immunotherapy when encapsulated with PTX to achieve enhanced chemoimmunotherapy. The off-coating strategy developed by natural products SM, provide a brand-new perspective to optimize CM-NPs, and it also embodies application value of "unification of medicines and excipients" of natural products.
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http://dx.doi.org/10.1002/adhm.202100311DOI Listing
May 2021

Establishment and Application of a Dual TaqMan Real-Time PCR Method for and .

Pol J Microbiol 2020 Sep 25;69(3):293-300. Epub 2020 Aug 25.

Chongqing Academy of Animal Science, Chongqing, China.

species are common opportunistic bacteria and foodborne pathogens. The proper detection of can effectively reduce the occurrence of food-borne public health events. and are the two most important pathogens in the genus. In this study, a dual TaqMan Real-Time PCR method was established to simultaneously detect and distinguish and in samples. The method exhibited good specificity, stability, and sensitivity. Specifically, the minimum detection concentrations of and in pure bacterial cultures were 6.08 × 10 colony forming units (CFU)/ml and 4.46 × 10 CFU/ml, respectively. Additionally, the minimum detectable number of and in meat and milk was 10 CFU/g. In addition, the method can be used to distinguish between strains of and within two hours. Overall, it is a sensitive, easy-to-use, and practical test for the identification and classification of in food.
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http://dx.doi.org/10.33073/pjm-2020-032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810114PMC
September 2020

Identification and construction of a novel biomimetic delivery system of paclitaxel and its targeting therapy for cancer.

Signal Transduct Target Ther 2021 Jan 27;6(1):33. Epub 2021 Jan 27.

Institute of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, 200041, China.

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http://dx.doi.org/10.1038/s41392-020-00390-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840929PMC
January 2021

Engineered liposomes targeting the gut-CNS Axis for comprehensive therapy of spinal cord injury.

J Control Release 2021 Mar 22;331:390-403. Epub 2021 Jan 22.

Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China. Electronic address:

Effective curative therapies for spinal cord injury (SCI), which is often accompanied by intestinal complications, are lacking. Potential therapeutic targets include astrocytes and their enteric nervous system counterpart, enteric glial cells (EGCs). Based on shared biomarkers and similar functions of both cell types, we designed an orally administered targeted delivery system in which the neuropeptide apamin, stabilized by sulfur replacement with selenium, was adopted as a targeting moiety, and the liposome surface was protected with a non-covalent cross-linked chitosan oligosaccharide lactate layer. The system effectively permeated through oral absorption barriers, targeted local EGCs and astrocytes after systemic circulation, allowing for comprehensive SCI therapy. Given the involvement of the gut-organ axis in a growing number of diseases, our research may shed light on new aspects of the oral administration route as a bypass for multiple interventions and targeted therapy.
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http://dx.doi.org/10.1016/j.jconrel.2021.01.032DOI Listing
March 2021

Strategies of Drug Delivery for Deep Fungal Infection: A Review.

Pharm Nanotechnol 2020 ;8(5):372-390

College of Pharmaceutical Sciences, Medical Research Institute, Southwest University, Chongqing, China.

The deep fungal infection poses serious threats to human health, mainly due to the increase in the number of immunocompromised individuals. Current first-line antifungal agents such as Amphotericin B, Fluconazole and Itraconazole, may decrease the severity of fungal infection to some extent, but the poor drug bioavailability, drug toxicity and poor water solubility seriously restrict their clinical utility. This review focuses on the study of drug delivery strategies for the treatment of deep fungal infections. We summarize the drug delivery strategies recently reported for the treatment of deep fungal infection, and explain each part with research examples. We discuss the use of pharmaceutical approaches to improve the physicochemical properties of the antifungal drugs to provide a basis for the clinical application of antifungal drugs. We then highlight the strategies for targeting drug delivery to the infection sites of fungi and fungal surface moieties, which have the potential to get developed as clinically relevant targeted therapies against deep fungal infections. It is worth noting that the current research on fungal infections still lags behind the research on other pathogens, and the drug delivery strategy for the treatment of deep fungal infections is far from meeting the treatment needs. Therefore, we envision the potential strategies inspired by the treatment of diseases with referential pathology or pathophysiology, further enriching the delivery of antifungal agents, providing references for basic research of fungal infections. Lay Summary: The deep fungal infections pose serious threats to the health of immunodeficiency patients. It is worth noting that the current research on fungi is still lagging behind that on other pathogens. The drug delivery strategies for the treatment of deep fungal infections are far from meeting the treatment needs. We summarize the recently reported drug delivery strategies for treating deep fungal infection, and envision the potential strategies to further enrich the delivery of antifungal agents.
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http://dx.doi.org/10.2174/2211738508666200910101923DOI Listing
January 2020

Anisotropic active ligandations in siRNA-Loaded hybrid nanodiscs lead to distinct carcinostatic outcomes by regulating nano-bio interactions.

Biomaterials 2020 Apr 3;251:120008. Epub 2020 Apr 3.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China; Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China. Electronic address:

Active targeting modification is one of the foremost nanomedicine strategies for the efficacy improvement. Compared to the homogeneous ligandation on spherical nanocarriers, non-spherical nanomedicines usually make the ligand modification more complicated. The modified ligands always exhibit anisotropy and heterogeneity. However, there is very little systematic study on these diversified anisotropic modifications. The efficacy difference and underlying mechanism were still unclear. Here, we separately fabricated hybrid nanodiscs (NDs) conjugated with cRGD on the edge and plane surfaces to engineer two anisotropic targeting nanocarriers (E-cRGD-NDs and P-cRGD-NDs, respectively) for gene delivery. The ligand anisotropy endowed NDs with diversified cellular interactions, and caused different efficacies between E-cRGD-NDs and P-cRGD-NDs. Of note, E-cRGD-NDs showed significant superiority in siRNA loading, cellular uptake, silence efficiency, protein expression and even in vivo efficacy. The mechanism investigation revealed the functional anisotropy specifically for E-cRGD-NDs. The edge modification of cRGD efficiently separated the targeting and siRNA loading domains, maximizing their respective functions. These findings reflected the unique effect of ligand anisotropy, also provided a new strategy for the targeting screening of extensive nanomedicines.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120008DOI Listing
April 2020

Overcoming the Reticuloendothelial System Barrier to Drug Delivery with a "Don't-Eat-Us" Strategy.

ACS Nano 2019 11 7;13(11):13015-13026. Epub 2019 Nov 7.

Key Laboratory of Luminescent and Real-Time Analytical Chemistry, Ministry of Education, College of Pharmaceutical Sciences , Southwest University , Chongqing 400715 , P.R. China.

Overcoming the reticuloendothelial system (RES) has long been a vital challenge to nanoparticles as drug carriers. Modification of nanoparticles with polyethylene glycol helps them avoid clearance by macrophages but also suppresses their internalization by target cells. To overcome this paradox, we developed an RES-specific blocking system utilizing a "don't-eat-us" strategy. First, a CD47-derived, enzyme-resistant peptide ligand was designed and placed on liposomes (d-self-peptide-labeled liposome, DSL). After mainline administration, DSL was quickly adsorbed onto hepatic phagocyte membranes (including those of Kupffer cells and liver sinusoidal endothelial cells), forming a long-lasting mask that enclosed the cell membranes and thus reducing interactions between phagocytes and subsequently injected nanoparticles. Compared with blank conventional liposomes (CL), DSL blocked the RES at a much lower dose, and the effect was sustained for a much longer time, highly prolonging the elimination half-life of the subsequently injected nanoparticles. This "don't-eat-us" strategy by DSL was further verified on the brain-targeted delivery against a cryptococcal meningitis model, providing dramatically enhanced brain accumulation of the targeted delivery system and superior therapeutic outcome of model drug Amphotericin B compared with CL. Our study demonstrates a strategy that blocks the RES by masking phagocyte surfaces to prolong nanoparticle circulation time without excess modification and illustrates its utility in enhancing nanoparticle delivery.
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http://dx.doi.org/10.1021/acsnano.9b05679DOI Listing
November 2019

Oriented Assembly of Cell-Mimicking Nanoparticles via a Molecular Affinity Strategy for Targeted Drug Delivery.

ACS Nano 2019 05 29;13(5):5268-5277. Epub 2019 Apr 29.

Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences , Southwest University , Chongqing , 400715 , China.

Cell membrane cloaking is an emerging field in drug delivery in which specific functions of parent cells are conferred to newly formed biomimetic vehicles. A growing variety of delivery systems with diverse surface properties have been utilized for this strategy, but it is unclear whether the affinity of membrane-core pairs could guarantee effective and proper camouflaging. In this study, we propose a concise and effective "molecular affinity" strategy using the intracellular domain of transmembrane receptors as "grippers" during membrane coating. Red blood cell (RBC) membranes and cationic liposomes were adopted for fabrication, and a peptide ligand derived from the cytoplasmic protein P4.2 was prepared to specifically recognize the cytoplasmic domain of band 3, a key transmembrane receptor of erythrocytes. Once anchored onto the liposome surface, the P4.2-derived peptide would interact with the isolated RBC membrane, forming a "hidden peptide button", which ensures the right-side-out orientation. The membrane-coated liposomes exhibited an appropriate size distribution around 100 nm and high stability, with superior circulation durations compared with those of conventional PEGylated liposomes. Importantly, they possessed the ability to target Candida albicans by the interaction between the pathogenic fungus and host erythrocytes and to neutralize hemotoxin secreted by the pathogenic fungi. The curative effect of the model drug was thus substantially improved. In summary, the "molecular affinity" strategy may provide a powerful and universal approach for the construction of cell membrane-coated biomaterials and nanomedicines at both laboratory and industrial scales.
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http://dx.doi.org/10.1021/acsnano.8b09681DOI Listing
May 2019

Nanoparticles Targeted against Cryptococcal Pneumonia by Interactions between Chitosan and Its Peptide Ligand.

Nano Lett 2018 10 1;18(10):6207-6213. Epub 2018 Oct 1.

Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences , Southwest University , Chongqing 400715 , P. R. China.

Inspired by the fact that chitosan is a representative constituent of the ectocellular structure of Cryptococcus neoformans and a typical biomaterial for improving drug oral absorption, we designed an elegant and efficient C. neoformans-targeted drug delivery system via oral administration. A chitosan-binding peptide screened by phage display was used as the targeting moiety, followed by conjugation to the surface of poly(lactic- co-glycolic acid) nanoparticles as the drug carrier, which was then incubated with free chitosan. The noncovalently bound chitosan adheres to mucus layers and significantly enhances penetration of nanoparticles through the oral absorption barrier into circulation and then re-exposed the targeting ligand for later recognition of the fungal pathogen at the site of infection. After loading itraconazole as a model drug, our drug delivery system remarkably cleared lung infections of C. neoformans and increased survival of model mice. Currently, targeted drug delivery is mainly performed intravenously; however, the system described in our study may provide a universal means to facilitate drug targeting to specific tissues and disease sites by oral administration and may be especially powerful in the fight against increasingly severe fungal infections.
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http://dx.doi.org/10.1021/acs.nanolett.8b02229DOI Listing
October 2018

Porphyrin-grafted Lipid Microbubbles for the Enhanced Efficacy of Photodynamic Therapy in Prostate Cancer through Ultrasound-controlled Accumulation.

Theranostics 2018 12;8(6):1665-1677. Epub 2018 Feb 12.

Department of Medical Ultrasonic, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.

Photodynamic therapy (PDT) holds promise for focal therapy of prostate cancer (PCa). However, the therapeutic efficacy needs improvement, and further development of PDT for PCa has challenges, including uncertainty of photosensitizers (PSs) accumulation at the tumor site and difficulty in visualizing lesions using conventional ultrasound (US) imaging. We have developed novel porphyrin-grafted lipid (PGL) microbubbles (MBs; PGL-MBs) and propose a strategy to integrate PGL-MBs with US imaging to address these limitations and enhance PDT efficacy.

Methods: PGL-MBs have two functions: imaging guidance by contrast-enhanced ultrasound (CEUS) and targeted delivery of PSs by ultrasound targeted microbubble destruction (UTMD). PGL-MBs were prepared and characterized before and after low-frequency US (LFUS) exposure. Then, studies validated the efficacy of PDT with PGL-MBs in human prostate cancer PC3 cells. PC3-xenografted nude mice were used to validate CEUS imaging, accumulation at the tumor site, and PDT efficacy.

Results: PGL-MBs showed good contrast enhancement for US imaging and were converted into nanoparticles upon LFUS exposure. The resulting uniquely structured nanoparticles avoided porphyrin fluorescence quenching and efficiently accumulated at the tumor site through the sonoporation effect created with the assistance of US to achieve excellent PDT efficacy.

Conclusions: This is the first preclinical investigation of MBs applied in PDT for PCa. PGL-MBs possess favorable CEUS imaging effects to enhance the localization of tumors. PGL-MBs with LFUS control PS accumulation at the tumor site to achieve highly effective PDT of PCa. This strategy carries enormous clinical potential for PCa management.
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http://dx.doi.org/10.7150/thno.22469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858174PMC
January 2019

A comparative study of the antitumor efficacy of peptide-doxorubicin conjugates with different linkers.

J Control Release 2018 04 2;275:129-141. Epub 2018 Feb 2.

Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China. Electronic address:

The peptide-drug conjugates caused much attention currently. The purpose of present study was to elucidate the possible synergistic effect between ligand peptide and stimuli-responsive linkage in amphiphilic peptide-drug conjugates (APDCs) with different linkers. Especially, the superiority of each strategy as well as the synergistic effect between them was carefully investigated via the parallel comparisons of the three systems throughout of the whole study. Here, we synthesized three APDCs, namely, cRGD-SS-DOX (RSSDOX), cRGD-S-DOX (RSDOX) and cRGD-VC-DOX (RVCDOX), using doxorubicin (DOX) as a model cytotoxic agent, cRGDfC as a homing peptide, and reduction cleavable disulfide (SS), noncleavable single thioether (S) or cathepsin B cleavable valine-citrulline dipeptide (VC) as linker. The APDCs showed high drug loading capacity and they were evaluated in vitro in the integrin αvβ3-overexpressing B16 cells and in vivo in tumor-bearing C57BL/6 mice. Endocytosis mechanism assay demonstrated that three types of APDCs internalized into cells through adynamin and actin depolymerizing-mediated pathway following receptor-mediated endocytosis. Notably, RSDOX or RVCDOX induced stronger antitumor efficacy, which depended on their cellular uptake levels, intracellular trafficking and the colocalization rates with lysosomes. The in vivo efficacy of RSDOX or RVCDOX was 1.4-1.7 fold of free DOX and 1.7-2.0 fold of RSSDOX, respectively. In addition, RSDOX or RVCDOX demonstrated acceptable system, tissue and blood compatibility. The compromised efficacy of RSSDOX might be due to the generation of DOX-SH during degradation of prodrug, but not DOX. Taken together, our studies suggest that certain type of APDCs can significantly decrease the toxicity of free DOX and improve therapy outcome, which provides insight for the design of peptide-drug conjugates integrating ligand peptide and stimuli-responsive linkage.
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http://dx.doi.org/10.1016/j.jconrel.2018.01.033DOI Listing
April 2018

A Nanosystem of Amphiphilic Oligopeptide-Drug Conjugate Actualizing Both αvβ3 Targeting and Reduction-Triggered Release for Maytansinoid.

Theranostics 2017 23;7(13):3306-3318. Epub 2017 Jul 23.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

To design a prodrug-based self-assembling nanosystem with both ligand targeting and stimuli-responsive features, and elucidate the superiority of each targeting strategy and the synergistic effect between them, we synthesized four small molecule amphiphilic peptide-drug conjugates (APDCs) using maytansinoid (DM1) as a cytotoxic agent, cRGDfK as a homing peptide, and disulfide (SS) or thioether (SMCC) as linker. Owing to their amphiphilicity, the APDCs could self-assemble into nanoparticles ([email protected]) which were evaluated in three different cell lines and in tumor-bearing C57BL/6 mice. The [email protected] showed the strongest interaction with αvβ3 integrin, highest cell uptake and intracellular free drug level, and best antitumor efficacy and , while it shared the same goodness with other test nanosystems in terms of high drug loading, EPR effect and free of potentially toxic polymers. Especially, the efficacy of [email protected] was 2 fold of free DM1 which is too cytotoxic to be a drug, while the active targeted [email protected] demonstrated acceptable system, tissue and blood compatibility. In αvβ3-positive cells or tumors, the RGD targeting contributed much more than disulfide in anticancer effect. The maximum synergism of the two strategies reached to 22 fold and 3 fold . Generally, the active targeting, prodrug and nanosystem could significantly decrease the toxicity of free DM1 and improve its therapy outcome via combining active targeting, prodrug and nanopreparation, especially the dual targeting strategies and their synergism.
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http://dx.doi.org/10.7150/thno.20242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595133PMC
July 2018

Combination antitumor therapy with targeted dual-nanomedicines.

Adv Drug Deliv Rev 2017 06 7;115:23-45. Epub 2017 Mar 7.

Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100191, China. Electronic address:

Combination therapy is one of the important treatment strategies for cancer at present. However, the outcome of current combination therapy based on the co-administration of conventional dosage forms is suboptimal, due to the short half-lives of chemodrugs, their deficient tumor selectivity and so forth. Nanotechnology-based targeted delivery systems show great promise in addressing the associated problems and providing superior therapeutic benefits. In this review, we focus on the combination of therapeutic strategies between different nanomedicines or drug-loaded nanocarriers, rather than the co-delivery of different drugs via a single nanocarrier. We introduce the general concept of various targeting strategies of nanomedicines, present the principles of combination antitumor therapy with dual-nanomedicines, analyze their advantages and limitations compared with co-delivery strategies, and overview the recent advances of combination therapy based on targeted nanomedicines. Finally, we reviewed the challenges and future perspectives regarding the selection of therapeutic agents, targeting efficiency and the gap between the preclinical and clinical outcome.
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http://dx.doi.org/10.1016/j.addr.2017.03.001DOI Listing
June 2017

Modulating Drug Release Rate from Partially Silica-Coated Bicellar Nanodisc by Incorporating PEGylated Phospholipid.

Bioconjug Chem 2017 01 17;28(1):53-63. Epub 2016 Oct 17.

Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, College of Engineering, School of Pharmaceutical Sciences, Peking University , Beijing 100871, China.

This article reports an effective method to regulate hydrophobic drug release rate from partially silica-coated bicellar nanodisc generated from proamphiphilic organoalkoxysilane and dihexanoylphosphatidylcholine by introducing different molar percentages of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 (DSPE-PEG2000) into planar bilayers of hybrid bicelles. It was found that the drug release rate increased with increasing the molar percentages of DSPE-PEG2000, and 57.38%, 69.21%, 78.69%, 81.64%, and 82.23% of hydrophobic doxorubicin was released within 120 h from the nanodics incorporating with 0%, 2.5%, 5%, 10%, and 20% DSPE-PEG2000, respectively. Compared with the non-PEGylated nanodisc and free doxorubicin, the PEGylated nanodiscs showed good biocompatibility, high cellular uptake, and adhesion, as well as high local drug accumulation. In addition, both in vitro and in vivo results demonstrated significantly improved antitumor efficacy of the PEGylated nanodisc than its control groups. Thus, the PEGylated nanodisc with partial silica coating offers a facile and efficient strategy of drug delivery for chemotherapy with improved patient acceptance and compliance.
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http://dx.doi.org/10.1021/acs.bioconjchem.6b00508DOI Listing
January 2017

A nanomedicine based combination therapy based on QLPVM peptide functionalized liposomal tamoxifen and doxorubicin against Luminal A breast cancer.

Nanomedicine 2016 Feb 19;12(2):387-97. Epub 2015 Dec 19.

Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China. Electronic address:

Unlabelled: Though combination chemotherapy or antitumor nanomedicine is extensively investigated, their combining remains in infancy. Additionally, enhanced delivery of estrogen or its analogs to tumor with highly-expressed estrogen-receptor (ER) is seldom considered, despite its necessity for ER-positive breast cancer treatment. Here, nanomedicine based combination therapy using QLPVM conjugated liposomal tamoxifen (TAM) and doxorubicin (DOX) was designed and testified, where the penta-peptide was derived from Ku70 Bax-binding domain. Quantitative, semi-quantitative and qualitative approaches demonstrated the enhanced endocytosis and cytotoxicity of QLPVM conjugated sterically stabilized liposomes (QLPVM-SSLs) in vitro and in vivo. Mechanism studies of QLPVM excluded the possible electrostatic, hydrophobic or receptor-ligand interactions. However, as a weak cell-penetrating peptide, QLPVM significantly induced drug release from QLPVM-SSLs during their interaction with cells, which was favorable for drug internalization. These findings suggested that the nanomedicine based combination therapy using QLPVM-SSL-TAM and QLPVM-SSL-DOX might provide a rational strategy for Luminal A breast cancer.

From The Clinical Editor: Breast cancer remains a leading cause of mortality in women worldwide. Although combined therapy using hormonal antagonist and chemotherapy is the norm nowadays, the use of these agents together in a single delivery system has not been tested. Here, the authors investigated this approach using QLPVM conjugated liposomes in in-vitro and in-vivo models. The positive findings may provide a novel direction for breast cancer treatment in the near future.
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http://dx.doi.org/10.1016/j.nano.2015.12.360DOI Listing
February 2016

A folate modified pH sensitive targeted polymeric micelle alleviated systemic toxicity of doxorubicin (DOX) in multi-drug resistant tumor bearing mice.

Eur J Pharm Sci 2015 Aug 25;76:95-101. Epub 2015 Apr 25.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. Electronic address:

Purpose: The purpose of this work was to demonstrate the advantages of a folate modified pH sensitive micelle system (HPPF) on reducing the systemic toxicity of antitumor drug doxorubicin (DOX) as well as increasing the antitumor efficacy on multi-drug resistant tumor.

Methods: The micelle HPPF was fabricated by PHIS-PEG and Fol-PEG-PLA using dialysis method. Multi-drug resistant human breast-cancer cell (MCF-7Adr) was used to test the therapeutic effect of DOX loaded HPPF micelles (HPPF/DOX). Nude mice bearing MCF-7Adr tumor was used to evaluate the systemic toxicity of HPPF/DOX.

Results: The micelle HPPF was successfully prepared with good size uniformity and pH sensitivity. The in vitro experiments showed that HPPF significantly increased the intracellular level and cytotoxicity of DOX. The in vivo experiments demonstrated that HPPF had largely reduced the mortality and body weight loss, improved the animal status and decreased damages on heart and lung tissues comparing to free DOX.

Conclusions: The HPPF/DOX could significantly increase the antitumor efficacy of DOX and largely alleviate the systemic side effects induced by high dose DOX in the treatment of multi-drug resistant tumor.
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http://dx.doi.org/10.1016/j.ejps.2015.04.018DOI Listing
August 2015