Publications by authors named "Xinlong Zang"

11 Publications

  • Page 1 of 1

Targeting macrophages using nanoparticles: a potential therapeutic strategy for atherosclerosis.

J Mater Chem B 2021 Apr 30;9(15):3284-3294. Epub 2021 Mar 30.

School of Basic Medicine, Qingdao University, Ningxia Road 308, Qingdao, P. R. China.

Atherosclerosis is one of the leading causes of vascular diseases, with high morbidity and mortality worldwide. Macrophages play a critical role in the development and local inflammatory responses of atherosclerosis, contributing to plaque rupture and thrombosis. Considering their central roles, macrophages have gained considerable attention as a therapeutic target to attenuate atherosclerotic progression and stabilize existing plaques. Nanoparticle-based delivery systems further provide possibilities to selectively and effectively deliver therapeutic agents into intraplaque macrophages. Although challenges are numerous and clinical application is still distant, the design and development of macrophage-targeting nanoparticles will generate new knowledge and experiences to improve therapeutic outcomes and minimize toxicity. Hence, the review aims to discuss various strategies for macrophage modulation and the development and evaluation of macrophage targeting nanomedicines for anti-atherosclerosis.
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http://dx.doi.org/10.1039/d0tb02956dDOI Listing
April 2021

Stimuli-responsive nanoparticles based on poly acrylic derivatives for tumor therapy.

Int J Pharm 2021 Mar 31;601:120506. Epub 2021 Mar 31.

School of Basic Medicine, Qingdao University, Ningxia Road 308, Qingdao, PR China. Electronic address:

Serve side effects caused by discriminate damage of chemotherapeutic drugs to normal cell and cancer cells remain a main obstacle in clinic. Hence, continuous efforts have been made to find ways to effectively enhance drug delivery and reduce side effects. Recent decades have witnessed impressive progresses in fighting against cancer, with improved understanding of tumor microenvironment and rapid development in nanoscale drug delivery system (DDS). Nanocarriers based on biocompatible materials provide possibilities to improve antitumor efficiency and minimize off-target effects. Among all kinds of biocompatible materials applied in DDS, polymeric acrylic derivatives such as poly(acrylamide), poly(acrylic acid), poly(N-isopropylacrylamide) present inherent biocompatibility and stimuli-responsivity, and relatively easy to be functionalized. Furthermore, nanocarrier based on polymeric acrylic derivatives have demonstrated high drug encapsulation, improved uptake efficiency, prolonged circulation time and satisfactory therapeutic outcome in tumor. In this review, we aim to discuss recent progress in design and development of stimulus-responsive poly acrylic polymer based nanocarriers for tumor targeting drug delivery.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120506DOI Listing
March 2021

Dual-targeting tumor cells and tumor associated macrophages with lipid coated calcium zoledronate for enhanced lung cancer chemoimmunotherapy.

Int J Pharm 2021 Feb 15;594:120174. Epub 2020 Dec 15.

School of Basic Medicine, Qingdao University, Ningxia Road 308, Qingdao, PR China. Electronic address:

Lung cancer is the leading cause of cancer death among both men and women, and non-small cell lung cancer (NSCLC) accounts for almost 80% of such death. Tumor associated macrophage (TAMs) are abundant components in NSCLC. TAMs play critical roles in angiogenesis, immune escape and chemoresistance. Here we developed a dual-targeting drug delivery system (CaZOL@BMNPs) of zoledronate, which could bind to both tumor cells with overexpressed biotin receptors and macrophage mannose receptor (MMR) positive TAMs. The biotin- and mannose-modified lipid coated calcium zoledronate nanoparticles were preferentially internalized in both tumor cells and TAMs, and thereby inhibited their survivals. Our studies demonstrated that CaZOl@BMNPs treatment obviously reduced angiogenesis, reprogrammed immunosuppressive tumor microenvironment and eventually restrained tumor progression with negligible systemic toxicity. Collectively, CaZOL@BMNPs could be a promising approach by dual-targeting tumor cells and TAMs for NSCLS chemoimmunotherapy.
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http://dx.doi.org/10.1016/j.ijpharm.2020.120174DOI Listing
February 2021

Ischemia Reperfusion Injury: Opportunities for Nanoparticles.

ACS Biomater Sci Eng 2020 12 24;6(12):6528-6539. Epub 2020 Nov 24.

School of Basic Medicine, Qingdao University, Ningxia Road 308, Qingdao 110016, P.R. China.

Ischemia reperfusion (IR)-induced oxidative stress, accompanied by inflammatory responses, contributes to morbidity and mortality in numerous diseases such as acute coronary syndrome, stroke, organ transplantation, and limb injury. Ischemia results in profound hypoxia and tissue dysfunction, whereas subsequent reperfusion further aggravates ischemic tissue damage through inducing cell death and activating inflammatory responses. In this review, we highlight recent studies of therapeutic strategies against IR injury. Furthermore, nanotechnology offers significant improvements in this area. Hence, we also review recent advances in nanomedicines for IR therapy, suggesting them as potent and promising strategies to improve drug delivery to IR-injured tissues and achieve protective effects.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01197DOI Listing
December 2020

Targeted Delivery of Dasatinib to Deplete Tumor-Associated Macrophages by Mannosylated Mixed Micelles for Tumor Immunotherapy.

ACS Biomater Sci Eng 2020 10 16;6(10):5675-5684. Epub 2020 Sep 16.

School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016 PR China.

Tumor-associated macrophages (TAMs) are abundant in tumors and predominately show protumor M2-type fostering tumor progression. Specific depletion of TAMs is conceivably favorable for antitumor therapy. In this study, mannosylated mixed micelles (DAS-MMic) were developed to specifically deliver dasatinib (DAS) to eliminate TAMs for tumor immunotherapy. In vitro and in vivo results showed that DAS-MMic could effectively eradicate TAMs, decrease angiogenesis, reprogram the immunosuppressive tumor microenvironment, and finally suppress tumor progression. These data suggest the potential of direct elimination of TAMs by DAS-MMic for tumor immunotherapy.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01046DOI Listing
October 2020

Exosome-based nanocarriers as bio-inspired and versatile vehicles for drug delivery: recent advances and challenges.

J Mater Chem B 2019 04 13;7(15):2421-2433. Epub 2019 Mar 13.

Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, P. R. China.

Recent decades have witnessed the fast and impressive development of nanocarriers as a drug delivery system. Considering the safety, delivery efficiency and stability of nanocarriers, there are many obstacles in accomplishing successful clinical translation of these nanocarrier-based drug delivery systems. The gap has urged drug delivery scientists to develop innovative nanocarriers with high compatibility, stability and longer circulation time. Exosomes are nanometer-sized, lipid-bilayer-enclosed extracellular vesicles secreted by many types of cells. Exosomes serving as versatile drug vehicles have attracted increasing attention due to their inherent ability of shuttling proteins, lipids and genes among cells and their natural affinity to target cells. Attractive features of exosomes, such as nanoscopic size, low immunogenicity, high biocompatibility, encapsulation of various cargoes and the ability to overcome biological barriers, distinguish them from other nanocarriers. To date, exosome-based nanocarriers delivering small molecule drugs as well as bioactive macromolecules have been developed for the treatment of many prevalent and obstinate diseases including cancer, CNS disorders and some other degenerative diseases. Exosome-based nanocarriers have a huge prospect in overcoming many hindrances encountered in drug and gene delivery. This review highlights the advances as well as challenges of exosome-based nanocarriers as drug vehicles. Special focus has been placed on the advantages of exosomes in delivering various cargoes and in treating obstinate diseases, aiming to offer new insights for exploring exosomes in the field of drug delivery.
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http://dx.doi.org/10.1039/c9tb00170kDOI Listing
April 2019

Targeted Delivery of Zoledronate to Tumor-Associated Macrophages for Cancer Immunotherapy.

Mol Pharm 2019 05 22;16(5):2249-2258. Epub 2019 Apr 22.

School of Pharmacy , Shenyang Pharmaceutical University , Wenhua Road No. 103 , Shenyang 110016 , PR China.

Tumor-associated macrophages (TAMs) are recruited from circulatory monocytes by tumor-derived factors, which differentiate into macrophages residing in the tumor microenvironment. TAMs play critical roles in promoting angiogenesis, invasion, metastasis and immune escape, and the direct depletion of TAMs is a promising strategy for tumor immunotherapy. In this study, we developed lipid-coated calcium zoledronate nanoparticles (CaZol@pMNPs) containing conjugated mannose, which were sterically shielded with an extracellular pH-sensitive material. The NPs specifically targeted TAMs and induced their apoptosis in vitro and in vivo. In a S180 tumor-bearing mouse model, CaZol@pMNPs effectively depleted TAMs, markedly decreased angiogenesis, reduced immune suppression, and eventually restrained tumor growth without eliciting systemic effects. The collective data indicate the potential of the direct depletion of TAMs using CaZol@pMNPs for cancer immunotherapy.
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00261DOI Listing
May 2019

Targeted Delivery of miRNA 155 to Tumor Associated Macrophages for Tumor Immunotherapy.

Mol Pharm 2019 04 20;16(4):1714-1722. Epub 2019 Mar 20.

School of Pharmacy , Shenyang Pharmaceutical University , Shenyang 110016 , P. R. China.

Tumor associated macrophages (TAMs) are important components residing in the tumor microenvironment. They are immunosuppressive and promote tumor progression. Targeting TAMs and reprogramming their phenotype may be a promising strategy that can restore antitumor immune responses. In this study, we developed a microRNA delivery system based on lipid-coated calcium phosphonate nanoparticles (CaP/miR@pMNPs) containing conjugated mannose and sterically shielded with a pH-responsive material. The nanocarrier could respond to the low pH in the tumor microenvironment and expose mannose to promote cellular internalization in TAMs. The carrier could reactivate TAMs and reprogram their functions, reverse the immunosuppressive tumor microenvironment, and inhibit tumor growth in a tumor-bearing mouse model. In summary, redirecting the polarization of TAMs is a potential therapeutic strategy for tumor immunotherapy.
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00065DOI Listing
April 2019

Intracellular release of PluronicL64 unimers into MCF-7/ADR cells to overcome multidrug resistance by surface-modified PAMAM.

J Mater Chem B 2017 Jun 16;5(21):3970-3981. Epub 2017 May 16.

Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, P. R. China.

Multidrug resistance (MDR) has been a major obstacle to tumor chemotherapy. Pluronic unimers have been reported to be promising copolymers to reverse MDR, and the intracellular delivery of Pluronic unimers is a problem worth thinking. To exert the excellent reversal effect of Pluronic unimers, DOX-loaded G4.0 PAMAM was modified with PluronicL64 via cis-aconitic acid as a pH-sensitive linkage (PCPAMAM/DOX), which could release DOX and Pluronic unimers into cytoplasm. The Pluronic-modified PAMAM (PCPAMAM) exhibited favorable biocompatibility and pH-sensitivity. PCPAMAM/DOX showed a nano-scale size and a sustained in vitro release profile. Compared with a control formulation, PCPAMAM/DOX showed a higher reversal effect on MCF-7/ADR cells and enhanced intracellular drug accumulation. The results of P-gp activity, subcellular distribution of PluronicL64, the ATP level and mitochondrial transmembrane potential all illustrated that free Pluronic unimers could be released by PCPAMAM functioning as reversal agents. In conclusion, PCPAMAM could be a promising vehicle to enhance DOX accumulation by overcoming MDR in MCF-7/ADR cells. This work also provided an effective method to deliver Pluronic unimers into MDR cells.
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http://dx.doi.org/10.1039/c7tb00659dDOI Listing
June 2017

Nanoparticles for tumor immunotherapy.

Eur J Pharm Biopharm 2017 Jun 18;115:243-256. Epub 2017 Mar 18.

Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. Electronic address:

Although most researches and therapies have been focused on the tumor itself, it is becoming clear that immune cells can not only suppress tumor development but support and maintain their malignant type. Promising recent developments in immunology will provide opportunities for tumor-specific immunotherapy, which can orchestrate the patients immune system to target, fight and eradicate cancer cells without destroying healthy cells. However, antitumor immunity driven by self-immune system alone may be therapeutically insufficient. Developments in nanoparticle based drug delivery system can promote immunotherapy and re-educate immunosuppressive tumor microenvironment (TME), which provide promising strategies for cancer therapy. In this review, we will focus on nanoparticle-based immunotherapeutic approaches against cancer, ranging from nanovaccines, artificial antigen presenting cells (aAPCs) to nanoparticles reversing tumor immunosuppressive microenvironment.
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http://dx.doi.org/10.1016/j.ejpb.2017.03.013DOI Listing
June 2017

Anti-EphA10 antibody-conjugated pH-sensitive liposomes for specific intracellular delivery of siRNA.

Int J Nanomedicine 2016 17;11:3951-67. Epub 2016 Aug 17.

Department of Pharmaceutics, School of Pharmacy.

Therapeutic delivery of small interfering RNA (siRNA) is a major challenge that limits its potential clinical application. Here, a pH-sensitive cholesterol-Schiff base-polyethylene glycol (Chol-SIB-PEG)-modified cationic liposome-siRNA complex, conjugated with the recombinant humanized anti-EphA10 antibody (Eph), was developed as an efficient nonviral siRNA delivery system. Chol-SIB-PEG was successfully synthesized and confirmed with FTIR and (1)H-NMR. An Eph-PEG-SIB-Chol-modified liposome-siRNA complex (EPSLR) was prepared and characterized by size, zeta potential, gel retardation, and encapsulation efficiency. Electrophoresis results showed that EPSLR was resistant to heparin replacement and protected siRNA from fetal bovine serum digestion. EPSLR exhibited only minor cytotoxicity in MCF-7/ADR cells. The results of flow cytometry and confocal laser scanning microscopy suggested that EPSLR enhanced siRNA transfection in MCF-7/ADR cells. Intracellular distribution experiment revealed that EPSLR could escape from the endo-lysosomal organelle and release siRNA into cytoplasm at 4 hours posttransfection. Western blot experiment demonstrated that EPSLR was able to significantly reduce the levels of MDR1 protein in MCF-7/ADR cells. The in vivo study of DIR-labeled complexes in mice bearing MCF-7/ADR tumor indicated that EPSLR could reach the tumor site rather than other organs more effectively. All these results demonstrate that EPSLR has much potential for effective siRNA delivery and may facilitate its therapeutic application.
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http://dx.doi.org/10.2147/IJN.S107952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993279PMC
March 2017