HSP90 Inhibitor Encapsulated Photo-Theranostic Nanoparticles for Synergistic Combination Cancer Therapy

Lin, Tzu‐Yin; Guo, Wenchang; Long, Qilai; Ma, Ai-Hong; Liu, Qiangqiang; Zhang, Hongyong; Huang, Yee; Chandrasekaran, Siddarth; Pan, Chong‐Xian; Lam, Kit S.; Li, Yuanpei

doi:10.7150/thno.14882

Cited by 68 publications

(55 citation statements)

References 29 publications

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“…Therefore, combining 17-AAG with PDT may improve the efficiency of PDT. To achieve this goal, Lin et al (2016) developed a multifunctional nano-platform (Nanoporphyrin) for targeted delivery of heat, reactive oxygen species, and 17-AAG simultaneously to the tumor sites in transgenic and xenograft murine tumor models.…”

Section: Encapsulated 17-aag In Nanoparticlementioning

confidence: 99%

Spotlight on 17‐AAG as an Hsp90 inhibitor for molecular targeted cancer treatment

et al. 2019

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Hsp90 is a ubiquitous chaperone with important roles in the organization and maturation of client proteins that are involved in the progression and survival of cancer cells. Multiple oncogenic pathways can be affected by inhibition of Hsp90 function through degradation of its client proteins. That makes Hsp90 a therapeutic target for cancer treatment. 17‐allylamino‐17‐demethoxy‐geldanamycin (17‐AAG) is a potent Hsp90 inhibitor that binds to Hsp90 and inhibits its chaperoning function, which results in the degradation of Hsp90's client proteins. There have been several preclinical studies of 17‐AAG as a single agent or in combination with other anticancer agents for a wide range of human cancers. Data from various phases of clinical trials show that 17‐AAG can be given safely at biologically active dosages with mild toxicity. Even though 17‐AAG has suitable pharmacological potency, its low water solubility and high hepatotoxicity could significantly restrict its clinical use. Nanomaterials‐based drug delivery carriers may overcome these drawbacks. In this paper, we review preclinical and clinical research on 17‐AAG as a single agent and in combination with other anticancer agents. In addition, we highlight the potential of using nanocarriers and nanocombination therapy to improve therapeutic effects of 17‐AAG.

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Section: Encapsulated 17-aag In Nanoparticlementioning

confidence: 99%

Spotlight on 17‐AAG as an Hsp90 inhibitor for molecular targeted cancer treatment

et al. 2019

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“…For PCa and BC there is only a limited number of publications, some of which already have been mentioned above in conjunction with the presentation of the different type of NPs as well as different imaging and therapy options available for TNPs [1,131,230,345,358,476,477,478,592,593]. As TNPs combine into one nanovehicle both imaging and therapy, the presentation of selected representative examples below illustrate some of these combinations evaluated so far for PCa and BC.…”

Section: Theranostic Nanoparticles For Prostate and Breast Cancermentioning

confidence: 99%

Nanoparticles as Theranostic Vehicles in Experimental and Clinical Applications—Focus on Prostate and Breast Cancer

Elgqvist

2017

IJMS

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Prostate and breast cancer are the second most and most commonly diagnosed cancer in men and women worldwide, respectively. The American Cancer Society estimates that during 2016 in the USA around 430,000 individuals were diagnosed with one of these two types of cancers, and approximately 15% of them will die from the disease. In Europe, the rate of incidences and deaths are similar to those in the USA. Several different more or less successful diagnostic and therapeutic approaches have been developed and evaluated in order to tackle this issue and thereby decrease the death rates. By using nanoparticles as vehicles carrying both diagnostic and therapeutic molecular entities, individualized targeted theranostic nanomedicine has emerged as a promising option to increase the sensitivity and the specificity during diagnosis, as well as the likelihood of survival or prolonged survival after therapy. This article presents and discusses important and promising different kinds of nanoparticles, as well as imaging and therapy options, suitable for theranostic applications. The presentation of different nanoparticles and theranostic applications is quite general, but there is a special focus on prostate cancer. Some references and aspects regarding breast cancer are however also presented and discussed. Finally, the prostate cancer case is presented in more detail regarding diagnosis, staging, recurrence, metastases, and treatment options available today, followed by possible ways to move forward applying theranostics for both prostate and breast cancer based on promising experiments performed until today.

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“…For instance, magnetic Zn 0.4 Fe 2.6 O 4 nanoparticles were found to effectively overcome the thermoresistance in mild hyperthermia through geldanamcin, indicating a good potential to improve hyperthermia‐induced anticancer efficiency. [9a] It is desired to design a rational approach for achieving PTT‐based synergistic treatments with reduced thermoresistance,[9a,10] and thus the inhibition of overexpressed HSP90 might act as a potential strategy to overcome tumor thermoresistance for maximizing PTT efficiency. [9a,10a,b,11]…”

Section: Introductionmentioning

confidence: 99%

“…[11a] Presumably, this type of HSP90 inhibitors may also act on stressfully overexpressed HSP90 in tumor cells upon light exposure. [10a] Here, we report a rational fabrication of the micelles that can achieve mutual synergy of PTT and MTT for effective tumor ablation ( Scheme ). The micelles integrating photothermal Cypate and HSP90 inhibitor 17AAG (CA‐Micelles) generate distinct photothermal effect from Cypate through enhanced photothermal conversion efficiency, as well as pH‐dependent release and effective cytoplasmic translocation of 17AAG through reactive oxygen species (ROS) mediated lysosomal disruption caused from Cypate under irradiation.…”

Section: Introductionmentioning

confidence: 99%

Mutually Synergistic Nanoparticles for Effective Thermo‐Molecularly Targeted Therapy

Luo

Wang

Deng

et al. 2017

Adv Funct Materials

101

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Photothermal therapy (PTT) is of particular importance as a highly potent therapeutic modality in cancer therapy. However, a critical challenge still remains in the exploration of highly effective strategy to maximize the PTT efficiency due to tumor thermoresistance and thus frequent tumor recurrence. Here, a rational fabrication of the micelles that can achieve mutual synergy of PTT and molecularly targeted therapy (MTT) for tumor ablation is reported. The micelles generate both distinct photothermal effect from Cypate through enhanced photothermal conversion efficiency and pH-dependent drug release. The micelles further exhibit effective cytoplasmic translocation of 17-allylamino-17-demethoxygeldanamycin (17AAG) through reactive oxygen species mediated lysosomal disruption caused by Cypate under irradiation. Translocated 17AAG specifically bind with heat shock protein 90 (HSP90), thereby inhibiting antiapoptotic p-ERK1/2 proteins for producing preferable MTT efficiency through early apoptosis. Meanwhile, translocated 17AAG molecules further block stressfully overexpressed HSP90 under irradiation and thus inhibit the overexpression of p-Akt for achieving the reduced thermoresistance of tumor cells, thus promoting the PTT efficiency through boosting both early and late apoptosis of Cypate. Moreover, the micelles possess enhanced resistance to photobleaching, preferable cellular uptake, and effective tumor accumulation, thus facilitating mutually synergistic PTT/MTT treatments with tumor ablation. These findings represent a general approach for potent cancer therapy.

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HSP90 Inhibitor Encapsulated Photo-Theranostic Nanoparticles for Synergistic Combination Cancer Therapy

Cited by 68 publications

References 29 publications

Spotlight on 17‐AAG as an Hsp90 inhibitor for molecular targeted cancer treatment

Spotlight on 17‐AAG as an Hsp90 inhibitor for molecular targeted cancer treatment

Nanoparticles as Theranostic Vehicles in Experimental and Clinical Applications—Focus on Prostate and Breast Cancer

Mutually Synergistic Nanoparticles for Effective Thermo‐Molecularly Targeted Therapy

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