Tumor-targeted/reduction-triggered composite multifunctional nanoparticles for breast cancer chemo-photothermal combinational therapy

Yun Yang; Danrong Hu; Yi Lu; Bingyang Chu; Xinlong He; Yu Chen; Yao Xiao; Chengli Yang; Kai Zhou; Liping Yuan; Zhiyong Qian

doi:10.1016/j.apsb.2021.08.021

Tumor-targeted/reduction-triggered composite multifunctional nanoparticles for breast cancer chemo-photothermal combinational therapy

doi: 10.1016/j.apsb.2021.08.021

a. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center of Biotherapy, Chengdu 610041, China;
b. West China School of Pharmacy, Sichuan University, Chengdu 610041, China

基金项目:

This work was supported by the National Natural Science Foundation of China (NSFC31930067, NSFC31771096, and NSFC31700869), the National Key Research and Development Program of China (2017YFC1103502), the 135 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYGD18002, China), and the Post-Doctor Research Project, West China Hospital, Sichuan University (No.19HXBH099, China). The authors thank Dr. Zhongqin Yan from the West China School of Pharmacy, Sichuan University, China for the PAI observation and analysis of the data.

详细信息

通讯作者:
Zhiyong Qian,E-mail:zhiyongqian@scu.edu.cn

中图分类号: https://www.sciencedirect.com/science/article/pii/S2211383521003117/pdf?md5=c450d22e8b943677c6e7c08deab689a1&pid=1-s2.0-S2211383521003117-main.pdf
计量
- 文章访问数: 84
- HTML全文浏览量: 59
- PDF下载量: 0
- 被引次数: 0
出版历程
- 收稿日期: 2021-05-24
- 修回日期: 2021-07-09
- 录用日期: 2021-08-02
- 网络出版日期: 2023-03-17

Tumor-targeted/reduction-triggered composite multifunctional nanoparticles for breast cancer chemo-photothermal combinational therapy

a. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center of Biotherapy, Chengdu 610041, China;
b. West China School of Pharmacy, Sichuan University, Chengdu 610041, China

Funds:

摘要

摘要: Breast cancer has become the most commonly diagnosed cancer type in the world. A combination of chemotherapy and photothermal therapy (PTT) has emerged as a promising strategy for breast cancer therapy. However, the intricacy of precise delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Therefore, to ensure that the therapeutic agents are synchronously delivered to the tumor site for their synergistic effect, a multifunctional nanoparticle system (PCRHNs) is developed, which is grafted onto the prussian blue nanoparticles (PB NPs) by reduction-responsive camptothecin (CPT) prodrug copolymer, and then modified with tumor-targeting peptide cyclo(Asp-d-Phe-Lys-Arg-Gly) (cRGD) and hyaluronic acid (HA). PCRHNs exhibited nano-sized structure with good monodispersity, high load efficiency of CPT, triggered CPT release in response to reduction environment, and excellent photothermal conversion under laser irradiation. Furthermore, PCRHNs can act as a photoacoustic imaging contrast agent-guided PTT. In vivo studies indicate that PCRHNs exhibited excellent biocompatibility, prolonged blood circulation, enhanced tumor accumulation, allow tumor-specific chemo-photothermal therapy to achieve synergistic antitumor effects with reduced systemic toxicity. Moreover, hyperthermia-induced upregulation of heat shock protein 70 in the tumor cells could be inhibited by CPT. Collectively, PCRHNs may be a promising therapeutic way for breast cancer therapy.
- Breast cancer /
- Chem-photothermal combinational therapy /
- Camptothecin /
- Prussian blue nanoparticles /
- Reduction-responsive prodrugs
Abstract: Breast cancer has become the most commonly diagnosed cancer type in the world. A combination of chemotherapy and photothermal therapy (PTT) has emerged as a promising strategy for breast cancer therapy. However, the intricacy of precise delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Therefore, to ensure that the therapeutic agents are synchronously delivered to the tumor site for their synergistic effect, a multifunctional nanoparticle system (PCRHNs) is developed, which is grafted onto the prussian blue nanoparticles (PB NPs) by reduction-responsive camptothecin (CPT) prodrug copolymer, and then modified with tumor-targeting peptide cyclo(Asp-d-Phe-Lys-Arg-Gly) (cRGD) and hyaluronic acid (HA). PCRHNs exhibited nano-sized structure with good monodispersity, high load efficiency of CPT, triggered CPT release in response to reduction environment, and excellent photothermal conversion under laser irradiation. Furthermore, PCRHNs can act as a photoacoustic imaging contrast agent-guided PTT. In vivo studies indicate that PCRHNs exhibited excellent biocompatibility, prolonged blood circulation, enhanced tumor accumulation, allow tumor-specific chemo-photothermal therapy to achieve synergistic antitumor effects with reduced systemic toxicity. Moreover, hyperthermia-induced upregulation of heat shock protein 70 in the tumor cells could be inhibited by CPT. Collectively, PCRHNs may be a promising therapeutic way for breast cancer therapy.
- Breast cancer /
- Chem-photothermal combinational therapy /
- Camptothecin /
- Prussian blue nanoparticles /
- Reduction-responsive prodrugs

HTML全文

参考文献(78)

[1]	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71:209-249
[2]	Masuda N, Lee SJ, Im YH, Lee ES, Yokata I, Kuroi K, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. New Engl J Med 2007; 376:2147-2159
[3]	Alberro JA, Ballester B, Deulofeu P, Fabregas R, Liombart HA. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer:meta-analysis of individual patient data from ten randomised trials. Lancet Oncol 2018; 19:27-39
[4]	Qu Y, Chu B, Wei X, Lei M, Hu D, Zha R, et al. Redox/pH dual-stimuli responsive camptothecin prodrug nanogels for "on-demand" drug delivery. J Control Release 2019; 296:93-106
[5]	Li X, Yang X, Lin Z, Wang D, Mei D, He B, et al. 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; 76:95-101
[6]	Roduner E. Size matters:why nanomaterials are different. Chem Soc Rev 2006; 35:583-592
[7]	Zhou M, Zhang X, Xu X, Chen X, Zhang X. Doxorubicin@Bcl-2 siRNA core@shell nanoparticles for synergistic anticancer chemotherapy. ACS Appl Bio Mater 2018; 1:289-297
[8]	Ma W, Su H, Cheetham A, Zhang W, Wang Y, Kan Q, et al. Synergistic antitumor activity of a self-assembling camptothecin and capecitabine hybrid prodrug for improved efficacy. J Control Release 2017; 263:102-111
[9]	Chu B, Qu Y, He X, Hao Y, Yang C, Yang Y, et al. ROS-responsive camptothecin prodrug nanoparticles for on-demand drug release and combination of chemotherapy and photodynamic therapy. Adv Funct Mater 2020; 52:2005918
[10]	Hou S, Zhou S, Chen S, Lu Q. Polyphosphazene-based drug self-framed delivery system as a universal intelligent platform for combination therapy against multidrug-resistant tumors. ACS Appl Bio Mater 2020; 4:2284-2294
[11]	Wu Y, Lv S, Li Y, He H, Ji Y, Zheng M, et al. Co-delivery of dual chemo-drugs with precisely controlled, high drug loading polymeric micelles for synergistic anti-cancer therapy. Biomater Sci 2020; 3:949-959
[12]	Zhi D, Yang T, Justin O, Zhang S, Donnelly RF. Photothermal therapy. J Control Release 2020; 325:52-71
[13]	Li X, Lovell JF, Yoon J, Chen X. Clinical development and potential of photothermal and photodynamic therapies for cancer. Nat Rev Clin Oncol 2020; 17:657-674
[14]	Vankayala R, Hwang KC. Near-infrared-light-activatable nanomaterial-mediated phototheranostic nanomedicines:an emerging paradigm for cancer treatment. Adv Mater 2018; 30:1706320
[15]	Chen X, Zou J, Zhang K, Zhu J, Zhang Y, Zhu Z, et al. Photothermal/matrix metalloproteinase-2 dual-responsive gelatin nanoparticles for breastcancer treatment. Acta Pharm Sin B 2021; 11:271-282
[16]	Zhou J, Li M, Hou Y, Luo Z, Chen Q, Cao H, et al. Engineering of a nanosized biocatalyst for combined tumor starvation and low-temperature photothermal therapy. ACS Nano 2018; 12:2858-2872
[17]	Tao W, Ji X, Xu X, Islam MA, Li Z, Chen S, et al. Antimonene quantum dots:synthesis and application as near-infrared photothermal agents for effective cancer therapy. Angew Chem Int Ed 2017; 56:11896-11900
[18]	Ouyang J, Feng C, Ji X, Li L, Gutti HK, Kim NY, et al. 2D monoelemental germanene quantum dots:synthesis as robust photothermal agents for photonic cancer nanomedicine. Angew Chem Int Ed 2019; 58:13405-13410
[19]	Cai X, Jia X, Gao W, Zhang K, Ma M, Wang S, et al. A versatile nanotheranostic agent for efficient dual-mode imaging guided synergistic chemo-thermal tumor therapy. Adv Funct Mater 2015; 25:2520-2529
[20]	Hu K, Xie L, Zhang Y, Hanyu M, Yang Z, Nagatsu K, et al. Marriage of black phosphorus and Cu²⁺ as effective photothermal agents for PET-guided combination cancer therapy. Nat Commun 2020; 11:2778
[21]	Ulukan H, Swaan PW. Camptothecins-a review of their chemotherapeutic potential. Drugs 2002; 62:2039-2057
[22]	Dai M, Xu X, Song J, Fu S, Gou M, Luo F, et al. Preparation of camptothecin-loaded PCEC microspheres for the treatment of colorectal peritoneal carcinomatosis and tumor growth in mice. Cancer Lett 2011; 312:189-196
[23]	Zhang H, Zhu J, Chu B, Chen L, Shi K, Zhang L, et al. Preparation, characterization and in vivo antitumor evaluation of a micellar formulation of camptothecin prodrug. Nanosci Nanotechnol Lett 2017; 9:1755-1766
[24]	Bala V, Rao S, Boyd BJ, Prestidge CA. Prodrug and nanomedicine approaches for the delivery of the camptothecin analogue SN38. J Control Release 2013; 172:48-61
[25]	Wen Y, Wang Y, Liu X, Zhang W, Xiong X, Han Z, et al. Camptothecin-based nanodrug delivery systems. Cancer Biol Med 2017; 14:363-370
[26]	Botella P, Rivero-Buceta E. Safe approaches for camptothecin delivery:structural analogues and nanomedicines. J Control Release 2017; 247:28-54
[27]	Wang-Gillam A, Li C, Bodoky G, Dean A, Shan Y, Jameson G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1):a global, randomised, open-label, phase 3 trial. Lancet 2016; 387:545-557
[28]	Poveda A, Selle F, Hilpert F, Reuss A, Savarese A, Vergote I, et al. Bevacizumab combined with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan in platinum-resistant recurrent ovarian cancer:analysis by chemotherapy cohort of the randomized phase III AURELIA trial. J Clin Oncol 2015; 33:3836-3838
[29]	Shi L, Hu Y, Lin A, Ma C, Zhang C, Su Y, et al. Matrix metalloproteinase responsive nanoparticles for synergistic treatment of colorectal cancer simultaneous anti-angiogenesis and chemotherapy. Bioconjugate Chem 2016; 27:2943-2953
[30]	Yu H, He J, Lu Q, Huo D, Yuan S, Zhou Z, et al. Anti-Fas antibody conjugated nanoparticles enhancing the antitumor effect of camptothecin by activating the Fas-FasL apoptotic pathway. ACS Appl Mater Interfaces 2016; 8:29950-29959
[31]	Hu X, Hu J, Tian J, Ge Z, Zhang G, Luo K, et al. Polyprodrug amphiphiles:hierarchical assemblies for shape-regulated cellular internalization, trafficking, and drug delivery. J Am Chem Soc 2013; 135:17617-17629
[32]	Wang S, Yu G, Wang Z, Jacobson O, Tian R, Lin L, et al. Hierarchical tumor microenvironment-responsive nanomedicine for programmed delivery of chemotherapeutics. Adv Mater 2018; 30:1803926
[33]	Lee MH, Yang Z, Lim CW, Lee YH, Dongbang S, Kang C, et al. Disulfide- cleavage-triggered chemosensors and their biological applications. Chem Rev 2013; 113:5071-5109
[34]	Schafer FQ, Buettner GR. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radical Biol Med 2001; 30:1191-1212
[35]	Hu M, Furukawa S, Ohtani R, Sukegawa H, Nemoto Y, Reboul J, et al. Synthesis of prussian blue nanoparticles with a hollow interior by controlled chemical etching. Angew Chem Int Ed Engl 2012; 51:984-988
[36]	Buser HJ, Schwarzenbach D, Petter W, Ludi A. The crystal structure of prussian blue:Fe₄[Fe(CN)₆]₃·xH₂O. Inorg Chem 1977; 16:2704-2710
[37]	Busquets MA, Estelrich J. Prussian blue nanoparticles:synthesis, surface modification, and biomedical applications. Drug Discov Today 2020; 25:1431-1443
[38]	Liu Z, Liu J, Wang R, Du Y, Ren J, Qu X. An efficient nano-based theranostic system for multi-modal imaging-guided photothermal sterilization in gastrointestinal tract. Biomaterials 2015; 56:206-218
[39]	Zhu W, Gao M, Zhu Q, Chi B, Zeng L, Hu J, et al. Monodispersed plasmonic prussian blue nanoparticles for zero-background SERS/MRI-guided phototherapy. Nanoscale 2020; 6:3292-3301
[40]	Wang Y, Pang X, Wang J, Chen Y, Song Y, Sun Q, et al. Magnetically-targeted and near infrared fluorescence/magnetic resonance/photoacoustic imaging-guided combinational anti-tumor phototherapy based on polydopamine-capped magnetic prussian bluenanoparticles. J Mater Chem 2018; 6:2460-2473
[41]	Lv S, Miao Y, Liu D, Song F. Recent development of photothermal agents (PTAs) based on small organic molecular dyes. Chembiochem 2020; 21:2098-2110
[42]	Song X, Gong H, Liu T, Cheng L, Wang C, Sun X, et al. J-Aggregates of organic dye molecules complexed with iron oxide nanoparticles for imaging-guided photothermal therapy under 915 nm light. Small 2014; 10:4362-4370
[43]	Zheng M, Yue C, Ma Y, Gong P, Zhao P, Zheng C, et al. Single-step assembly of DOX/ICG loaded lipid-polymer nanoparticles for highly effective chemo-photothermal combination therapy. ACS Nano 2013; 7:2056-2067
[44]	Fernandes N, Rodrigues C, Moreira A, Corrria IJ. Overview of the application of inorganic nanomaterials in cancer photothermal therapy. Biomater Sci 2020; 8:2990-3020
[45]	Song X, Wang X, Yu S, Cao J, Li S, Li J, et al. Co₉Se₈ Nanoplates as a new theranostic platform for photoacoustic/magnetic resonance dual-modal-imaging-guided chemo-photothermal combination therapy. Adv Mater 2015; 27:3285-3291
[46]	Shao J, Xie H, Huang H, Li Z, Sun Z, Xu Y, et al. Biodegradable black phosphorus-based nanospheres for in vivo photothermal cancer therapy. Nat Commun 2016; 7:12967
[47]	Cheng L, Liu J, Gu X, Gong H, Shi X, Liu T, et al. PEGylated WS₂ nanosheets as a multifunctional theranostic agent for in vivo dual-modal CT/photoacoustic imaging guided photothermal therapy. Adv Mater 2014; 26:1886-1893
[48]	Yavuz MS, Cheng Y, Chen J, Cobley CM, Zhang Q, Rycenga M, et al. Gold nanocages covered by smart polymers for controlled release with near-infrared light. Nat Mater 2009; 8:935-939
[49]	Liang X, Deng Z, Jing L, Li X, Dai Z, Li C, et al. Prussian blue nanoparticles operate as a contrast agent for enhanced photoacoustic imaging. Chem Commun 2013; 49:11029-11031
[50]	Cheng L, Gong H, Zhu W, Liu J, Wang X, Liu G, et al. PEGylated prussian blue nanocubes as a theranostic agent for simultaneous cancer imaging and photothermal therapy. Biomaterials 2014; 35:9844-9852
[51]	Zhu W, Liu K, Sun X, Wang X, Li Y, Cheng L, et al. Mn²⁺-doped prussian blue nanocubes for bimodal imaging and photothermal therapy with enhanced performance. ACS Appl Mater Interfaces 2015; 7:11575-11582
[52]	Guo C, Jin Y, Dai Z. Multifunctional ultrasound contrast agents for imaging guided photothermal therapy. Bioconjug Chem 2014; 25:840-854
[53]	Peng J, Dong M, Ran B, Li W, Hao Y, Yang Q, et al. "One-for-All" -type, biodegradable prussian blue/manganese dioxide hybrid nanocrystal for trimodal imaging-guided photothermal therapy and oxygen regulation of breast cancer. ACS Appl Mater Interfaces 2017; 9:13875
[54]	Fu J, Wu B, Wei M, Huang Y, Zhou Y, Zhang Q, et al. Prussian blue nanosphere-embeddedin situhydrogel for photothermal therapy byperitumoral administration. Acta Pharm Sin B 2019; 9:604-614
[55]	Overchuk M, Zheng G. Overcoming obstacles in the tumor microenvironment:recent advancements in nanoparticle delivery for cancer theranostics. Biomaterials 2018; 156:217-237
[56]	Parodi A, Quattrocchi N, Van de Ven A, Chiappini C, Evangelopoulos M, Martinez J, et al. Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. Nat Nanotechnol 2013; 8:61-68
[57]	Liu Y, Wang Z, Liu Y, Zhu G, Jacobson O, Fu X, et al. Suppressing nanoparticle-mononuclear phagocyte system interactions of two-dimensional gold nanorings for improved tumor accumulation and photothermal ablation of tumors. ACS Nano 2017; 11:10539-10548
[58]	Garcia K, Zarschler K, Barbaro L, Barreto J, Malley WO, Spiccia L, et al. Zwitterionic-coated "stealth" nanoparticles for biomedical applications:recent advances in countering biomolecular corona formation and uptake by the mononuclear phagocyte system. Small 2014; 10:2516-2529
[59]	Danhier F, Le Breton A, Preat V. RGD-based strategies to target alpha(v)beta(3) integrin in cancer therapy and diagnosis. Mol Pharm 2012; 9:2961-2973
[60]	Xing F, Zhou C, Hui D, Du C, Wu L, Wang L, et al. Hyaluronic acid as a bioactive component for bone tissue regeneration:fabrication, modification, properties, and biological functions. Nanotechnol Rev 2020; 9:1059-1079
[61]	Ungelenk S, Moayed F, Ho CT, Grousl T, Scharf A, Mashaghi A, et al. Small heat shock proteins sequester misfolding proteins in near-native conformation for cellular protection and efficient refolding. Nat Commun 2016; 7:13673-13687
[62]	An Z, Tang W, Wu M, Jiao Z, Stucky GD. Hetero functional polymers and core-shell nanoparticles cascade aminolysis/michael addition and alkyne-azide click reaction of RAFT polymers. Chem Commun 2008; 48:6501-6503
[63]	Liu T, Liu S. Responsive polymers-based dual fluorescent chemosensors for Zn²⁺ ions and temperatures working in purely aqueous media. Anal Chem 2011; 83:2775-2785
[64]	Lai JT, Filla D, Shea R. Functional polymers from novel carboxyl-terminated trithiocarbonates as highly efficient RAFT agents. Macromolecules 2002; 35:6754-6756
[65]	Li Z, Hu Y, Jiang T, Howard KA, Li Y, Fan X, et al. Human-serum-albumin-coated prussian blue nanoparticles as pH-/thermotriggered drug-delivery vehicles for cancer thermochemotherapy. Part Part Syst Charact 2016; 33:53-62
[66]	Koppolu B, Zaharoff DA. The effect of antigen encapsulation in chitosan particles on uptake, activation and presentation by antigen presenting cells. Biomaterials 2013; 34:2359-2369
[67]	Getts D, Martin A, McCarthy D, Terry R, Hunter Z, Yap W, et al. Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis. Nat Biotechnol 2012; 30:1217-1224
[68]	Yu G, Yang Z, Fu X, Yung BC, Yang J, Mao Z, et al. Polyrotaxane-based supramolecular theranostics. Nat Commun 2018; 9:766
[69]	Yang K, Liu Y, Zhang Q, Kong C, Yi C, Zhou Z, et al. Cooperative assembly of magneto-nanovesicles with tunable wall thickness and permeability for MRI-guided drug delivery. J Am Chem Soc 2018; 140:4666-4677
[70]	Hsiang YH, Hertzberg R, Hecht S, Liu L. Camptothecin induces protein-linked DNA breaks mammalian DNA topoisomerase I. J Biol Chem 1985; 260:14873-14878
[71]	Zimmer A, Amar-Farkash S, Danon T, Alon U. Dynamic proteomics reveals bimodal protein dynamics of cancer cells in response to HSP90 inhibitor. BMC Syst Biol 2017; 11:33
[72]	Rowe TC, Couto E, Kroll DJ. Camptothecin inhibits HSP70 heat-shock transcription and induces DNA strand breaks in HSP70 genes in Drosophila. NCI Monogr. 1987; 4:49-53
[73]	Paduch R, Jakubowicz-Gil J, Niedziela P. Hepatocyte growth factor (HGF), heat shock proteins (HSPs) and multidrug resistance protein (MRP) expression in co-culture of colon tumor spheroids with normal cells after incubation with interleukin-1beta (IL-1beta) and/or camptothecin (CPT-11). Indian J Exp Biol 2010; 48:354-364
[74]	Liu S, Yuan Y, Okumura Y, Shinkai N, Yamauchi H. Camptothecin disrupts androgen receptor signaling and suppresses prostate cancer cell growth. Biochem Bioph Res Co 2010; 394:297-302
[75]	Elmallah M, Gordonnier M, Vautrot V, Chanteloup G, Garrido C, Gobbo J. Membrane-anchored heat-shock protein 70 (Hsp70) in cancer. Cancer Let 2020; 469:134-141
[76]	Yue X, Zhang Q, Dai Z. Near-infrared light-activatable polymeric nanoformulations for combined therapy and imaging of cancer. Adv Drug Delivery Rev 2017; 115:155-170
[77]	Zhang L, Zhang Y, Xue Y, Wu Y, Wang Q, Xue L, et al. Transforming weakness into strength:photothermal-therapy-induced inflammation enhanced cytopharmaceutical chemotherapy as a combination anticancer treatment. Adv Mater 2019; 31:1805936
[78]	Han R, Xiao Y, Yang Q, Pan M, Hao Y, He X, et al. Ag₂S nanoparticle-mediated multiple ablations reinvigorates the immune response for enhanced cancer photo-immunotherapy. Biomaterials 2012; 264:120451

施引文献

资源附件(0)

访问统计

点击查看大图

计量

文章访问数: 84
HTML全文浏览量: 59
PDF下载量: 0
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

留言板

Tumor-targeted/reduction-triggered composite multifunctional nanoparticles for breast cancer chemo-photothermal combinational therapy

doi: 10.1016/j.apsb.2021.08.021

通讯作者:
Zhiyong Qian,E-mail:zhiyongqian@scu.edu.cn

计量

Tumor-targeted/reduction-triggered composite multifunctional nanoparticles for breast cancer chemo-photothermal combinational therapy

计量

目录

留言板

Tumor-targeted/reduction-triggered composite multifunctional nanoparticles for breast cancer chemo-photothermal combinational therapy

doi: 10.1016/j.apsb.2021.08.021

通讯作者: Zhiyong Qian,E-mail:zhiyongqian@scu.edu.cn

计量

出版历程

Tumor-targeted/reduction-triggered composite multifunctional nanoparticles for breast cancer chemo-photothermal combinational therapy

计量

出版历程

目录

通讯作者:
Zhiyong Qian,E-mail:zhiyongqian@scu.edu.cn