Dual mode of cancer cell destruction for pancreatic cancer therapy using Hsp90 inhibitor loaded polymeric nano magnetic formulation

Rochani, Ankit; Beena, Sivakumar; Girija, Aswathy Ravindran; Raveendran, Sreejith; Borah, Ankita; Nagaoka, Yutaka; Nakajima, Yoshio; Maekawa, Toru; Kumar, D. Sakthi

doi:10.1016/j.ijpharm.2016.07.048

Cited by 31 publications

(25 citation statements)

References 38 publications

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“…In order to enhance the efficacy of 17- N -allylamino-17-demethoxygeldanamycin (17AAG), an HSP 90 inhibitor, against pancreatic cancer, Rochani et al (2016) established new nano formulations containing PLGA-coated, 17AAG- and Fe 3 O 4 -loaded magnetic NPs. The aqueous dispensable formulations were able to provide anti-pancreatic cancer activity in the MIA PaCa-2 cell line in a dose- and time-dependent manner in comparison to the murine fibroblast cell lines, L929 [ 84 ]. To improve oral bio-availability and efficacy in MDR breast cancer, PLGA NPs were loaded with a chemosensitizer (piperine, PIP) and rapamycin (RPM) formulated for sustained release and effective treatment.…”

Section: Types Of Nps Used For Combination Therapymentioning

confidence: 99%

Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer

Gurunathan

Kang

Qasim

et al. 2018

IJMS

271

133

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Cancer represents a group of heterogeneous diseases characterized by uncontrolled growth and spread of abnormal cells, ultimately leading to death. Nanomedicine plays a significant role in the development of nanodrugs, nanodevices, drug delivery systems and nanocarriers. Some of the major issues in the treatment of cancer are multidrug resistance (MDR), narrow therapeutic window and undesired side effects of available anticancer drugs and the limitations of anticancer drugs. Several nanosystems being utilized for detection, diagnosis and treatment such as theranostic carriers, liposomes, carbon nanotubes, quantum dots, polymeric micelles, dendrimers and metallic nanoparticles. However, nonbiodegradable nanoparticles causes high tissue accumulation and leads to toxicity. MDR is considered a major impediment to cancer treatment due to metastatic tumors that develop resistance to chemotherapy. MDR contributes to the failure of chemotherapies in various cancers, including breast, ovarian, lung, gastrointestinal and hematological malignancies. Moreover, the therapeutic efficiency of anticancer drugs or nanoparticles (NPs) used alone is less than that of the combination of NPs and anticancer drugs. Combination therapy has long been adopted as the standard first-line treatment of several malignancies to improve the clinical outcome. Combination therapy with anticancer drugs has been shown to generally induce synergistic drug actions and deter the onset of drug resistance. Therefore, this review is designed to report and analyze the recent progress made to address combination therapy using NPs and anticancer drugs. We first provide a comprehensive overview of the angiogenesis and of the different types of NPs currently used in treatments of cancer; those emphasized in this review are liposomes, polymeric NPs, polymeric micelles (PMs), dendrimers, carbon NPs, nanodiamond (ND), fullerenes, carbon nanotubes (CNTs), graphene oxide (GO), GO nanocomposites and metallic NPs used for combination therapy with various anticancer agents. Nanotechnology has provided the convenient tools for combination therapy. However, for clinical translation, we need continued improvements in the field of nanotechnology.

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Section: Types Of Nps Used For Combination Therapymentioning

confidence: 99%

Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer

Gurunathan

Kang

Qasim

et al. 2018

IJMS

271

133

View full text Add to dashboard Cite

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“…Since magnetic hyperthermia combined with 17‐AAG has promising effects against pancreatic cancer, Rochani et al. () prepared 17‐AAG and Fe 3 O 4 loaded magnetic NPs coated with PLGA to increase the efficacy of 17‐AAG. They indicated that combination of 17‐AAG and magnetic hyperthermia serve as a potential alternative treatment for pancreatic cancer.…”

Section: ‐Aag‐loaded Nanocarriersmentioning

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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“…In one report, heat shock of HUVECs before LPS treatment prevented apoptosis [72], but direct inhibition of HSP90 was not attempted. Most studies involving hyperthermia in combination with HSP90 inhibition have involved inhibitors encased in thermoresponsive nanopolymers [73–75], with few published studies of heat stress separate from drug treatment. The concurrent effects of hyperthermia and HSP90 inhibition on cell lines with mutated p53 did increase apoptosis of those cancer cells [76].…”

Section: Discussionmentioning

confidence: 99%

HSP90 inhibitors in the context of heat shock and the unfolded protein response: effects on a primary canine pulmonary adenocarcinoma cell line*

Graner

Hellwinkel

Lencioni

et al. 2016

International Journal of Hyperthermia

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Background Agents targeting HSP90 and GRP94 are seldom tested in stressed contexts such as heat shock (HS) or the unfolded protein response (UPR). Tumor stress often activates HSPs and the UPR as pro-survival mechanisms. This begs the question of stress effects on chemotherapeutic efficacy, particularly with drugs targeting chaperones such as HSP90 or GRP94. We tested the utility of several HSP90 inhibitors, including PU-H71 (targeting GRP94), on a primary canine lung cancer line under HS/UPR stress compared to control conditions. Methods We cultured canine bronchoalveolar adenocarcinoma cells that showed high endogenous HSP90 and GRP94 expression; these levels substantially increased upon HS or UPR induction. We treated cells with HSP90 inhibitors 17-DMAG, 17-AAG, or PU-H71 under standard conditions, HS, or UPR. Cell viability/survival were assayed. Antibody arrays measured intracellular signalling and apoptosis profiles. Results HS and UPR had varying effects on cells treated with different HSP90 inhibitors; in particular, HS and UPR promoted resistance to inhibitors in short-term assays, but combinations of UPR stress and PU-H571 showed potent cytotoxic activity in longer-term assays. Array data indicated altered signalling pathways, with apoptotic and pro-survival implications. UPR induction+dual targeting of HSP90 and GRP94 swayed the balance toward apoptosis. Conclusion Cellular stresses, endemic to tumors, or interventionally inducible, can deflect or enhance chemo-efficacy, particularly with chaperone-targeting drugs. Stress is likely not held accountable when testing new pharmacologics or assessing currently-used drugs. A better understanding of stress impacts on drug activities should be critical in improving therapeutic targeting and in discerning mechanisms of drug resistance.

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Dual mode of cancer cell destruction for pancreatic cancer therapy using Hsp90 inhibitor loaded polymeric nano magnetic formulation

Cited by 31 publications

References 38 publications

Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer

Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer

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

HSP90 inhibitors in the context of heat shock and the unfolded protein response: effects on a primary canine pulmonary adenocarcinoma cell line*

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