Tumor Targeting Chemo- and Photodynamic Therapy Packaged in Albumin for Enhanced Anti-Tumor Efficacy

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2020 Feb 6

PMID 32021171

Citations 2

Authors

Ke Zheng

Hongyan Liu

Xinxin Liu

Ying Wang

Linlin Li

Shijie Li

Jinping Xue

Mingdong Huang

Affiliations

Soon will be listed here.

Abstract

Purpose: Combination therapy for tumors is an important and promising strategy to improve therapeutic efficiency. This study aims at combining tumor targeting, chemo-, and photodynamic therapies to improve the anti-tumor performance.

Patients And Methods: Human serum albumin (HSA), as a nontoxic and biodegradable drug carrier, was used to load hydrophobic photosensitizers (mono-substituted β-4-pyridyloxy phthalocyanine zinc, mPPZ) by a dilution-incubation-purification (DIP) strategy to form molecular complex HSA:mPPZ. This complex was cross-linked as nanoparticles, and then chemotherapy drug doxorubicin (DOX) was adsorbed into the nanoparticles to achieve combined photodynamic therapy and chemotherapy. Next, the surface of the obtained composite was modified by a tumor surface receptor (urokinase receptor) targeting agent (ATF-HSA) using a noncovalent method to obtain the final product (ATF-HSA@HSA:mPPZ:DOX nanoparticles, AHmDN).

Results: AHmDN exhibited strong stability, remarkable cytotoxicity and higher uptake to tumor cells. Cell imaging analysis indicated that DOX was separated from AHmDN and uniformly distributed in cell nucleus while mPPZ localized in cytoplasm. The PDT activity of all the samples had been confirmed by the detection of intracellular ROS. In animal experiments, AHmDN was demonstrated to have a prominent tumor-targeting effect using a 3D imaging system. In addition, the enhanced antitumor effect of AHmDN in tumor-bearing mice was also been observed. Importantly, the tumor-targeting effect of such nanoparticles lasted for about 14 days after one injection.

Conclusion: These albumin nanoparticles with combined functions of tumor targeting, chemotherapy and photodynamic therapy can highly enhance the anti-tumor effect. This drug delivery system can be applied to package other hydrophobic photosensitizers and chemotherapy drugs for improving therapeutic efficacy to tumors.

Citing Articles

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An in vitro study of the effect of 5-ALA-mediated photodynamic therapy on oral squamous cell carcinoma.

Ma Y, Qu S, Xu L, Lu H, Li B BMC Oral Health. 2020; 20(1):258.

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References

Fan W, Yung B, Huang P, Chen X . Nanotechnology for Multimodal Synergistic Cancer Therapy. Chem Rev. 2017; 117(22):13566-13638. DOI: 10.1021/acs.chemrev.7b00258. View

Chen Q, Wang X, Wang C, Feng L, Li Y, Liu Z . Drug-Induced Self-Assembly of Modified Albumins as Nano-theranostics for Tumor-Targeted Combination Therapy. ACS Nano. 2015; 9(5):5223-33. DOI: 10.1021/acsnano.5b00640. View

Ghuman J, Zunszain P, Petitpas I, Bhattacharya A, Otagiri M, Curry S . Structural basis of the drug-binding specificity of human serum albumin. J Mol Biol. 2005; 353(1):38-52. DOI: 10.1016/j.jmb.2005.07.075. View

Meng H, Mai W, Zhang H, Xue M, Xia T, Lin S . Codelivery of an optimal drug/siRNA combination using mesoporous silica nanoparticles to overcome drug resistance in breast cancer in vitro and in vivo. ACS Nano. 2013; 7(2):994-1005. PMC: 3620006. DOI: 10.1021/nn3044066. View

Lopez J, Banerji U . Combine and conquer: challenges for targeted therapy combinations in early phase trials. Nat Rev Clin Oncol. 2016; 14(1):57-66. PMC: 6135233. DOI: 10.1038/nrclinonc.2016.96. View

Thorn C, Oshiro C, Marsh S, Hernandez-Boussard T, Mcleod H, Klein T . Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenet Genomics. 2010; 21(7):440-6. PMC: 3116111. DOI: 10.1097/FPC.0b013e32833ffb56. View

Hu D, Chen L, Qu Y, Peng J, Chu B, Shi K . Oxygen-generating Hybrid Polymeric Nanoparticles with Encapsulated Doxorubicin and Chlorin e6 for Trimodal Imaging-Guided Combined Chemo-Photodynamic Therapy. Theranostics. 2018; 8(6):1558-1574. PMC: 5858167. DOI: 10.7150/thno.22989. View

Huang J, Zhong X, Wang L, Yang L, Mao H . Improving the magnetic resonance imaging contrast and detection methods with engineered magnetic nanoparticles. Theranostics. 2012; 2(1):86-102. PMC: 3263519. DOI: 10.7150/thno.4006. View

Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394-424. DOI: 10.3322/caac.21492. View

10.

Liao J, Li W, Peng J, Yang Q, Li H, Wei Y . Combined cancer photothermal-chemotherapy based on doxorubicin/gold nanorod-loaded polymersomes. Theranostics. 2015; 5(4):345-56. PMC: 4329499. DOI: 10.7150/thno.10731. View

11.

Zhang W, Shen J, Su H, Mu G, Sun J, Tan C . Co-Delivery of Cisplatin Prodrug and Chlorin e6 by Mesoporous Silica Nanoparticles for Chemo-Photodynamic Combination Therapy to Combat Drug Resistance. ACS Appl Mater Interfaces. 2016; 8(21):13332-40. DOI: 10.1021/acsami.6b03881. View

12.

Wang B, Yu X, Wang J, Li Z, Li P, Wang H . Gold-nanorods-siRNA nanoplex for improved photothermal therapy by gene silencing. Biomaterials. 2015; 78:27-39. DOI: 10.1016/j.biomaterials.2015.11.025. View

13.

Di Corato R, Bealle G, Kolosnjaj-Tabi J, Espinosa A, Clement O, Silva A . Combining magnetic hyperthermia and photodynamic therapy for tumor ablation with photoresponsive magnetic liposomes. ACS Nano. 2015; 9(3):2904-16. DOI: 10.1021/nn506949t. View

14.

Li R, Zheng K, Hu P, Chen Z, Zhou S, Chen J . A novel tumor targeting drug carrier for optical imaging and therapy. Theranostics. 2014; 4(6):642-59. PMC: 3982134. DOI: 10.7150/thno.8527. View

15.

Lucky S, Soo K, Zhang Y . Nanoparticles in photodynamic therapy. Chem Rev. 2015; 115(4):1990-2042. DOI: 10.1021/cr5004198. View

16.

Zheng K, Li R, Zhou X, Hu P, Zhang Y, Huang Y . Dual actions of albumin packaging and tumor targeting enhance the antitumor efficacy and reduce the cardiotoxicity of doxorubicin in vivo. Int J Nanomedicine. 2015; 10:5327-42. PMC: 4554405. DOI: 10.2147/IJN.S84478. View

17.

Wan X, Min Y, Bludau H, Keith A, Sheiko S, Jordan R . Drug Combination Synergy in Worm-like Polymeric Micelles Improves Treatment Outcome for Small Cell and Non-Small Cell Lung Cancer. ACS Nano. 2018; 12(3):2426-2439. PMC: 5960350. DOI: 10.1021/acsnano.7b07878. View

18.

Dolmans D, Fukumura D, Jain R . Photodynamic therapy for cancer. Nat Rev Cancer. 2003; 3(5):380-7. DOI: 10.1038/nrc1071. View

19.

Li R, Zheng K, Yuan C, Chen Z, Huang M . Be Active or Not: the Relative Contribution of Active and Passive Tumor Targeting of Nanomaterials. Nanotheranostics. 2017; 1(4):346-357. PMC: 5646738. DOI: 10.7150/ntno.19380. View

20.

Elsadek B, Kratz F . Impact of albumin on drug delivery--new applications on the horizon. J Control Release. 2011; 157(1):4-28. DOI: 10.1016/j.jconrel.2011.09.069. View