Hsp90-targeted miRNA-liposomal formulation for systemic antitumor effect

Pore, Subrata K.; Choudhary, Ashwani; Rathore, Bhowmira; Ganguly, Anirban; Sujitha, Pombala; Kumar, C. Ganesh; Agawane, Sachin B.; Kumar, Jerald Mahesh; Scaria, Vinod; Pillai, Beena; Banerjee, Rajkumar

doi:10.1016/j.biomaterials.2013.05.054

Cited by 25 publications

(25 citation statements)

References 35 publications

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“…The DX-lipoplex containing this anticancer gene has been previously shown to exhibit excellent antitumor activity in mouse melanoma model. 32 The resulting lipoplex along with other treatment groups were treated to different cancer cells for 48 h. DX liposome had no effect on viability of cancer cells tested, but interestingly, when DX liposome was exposed to the cells in the lipoplex form (i.e., in association with amiR-Hsp90 or control plasmid), the lipoplex could reduce cellular viability (Figure 1C). We also observed that DX complexed with control plasmid of amiR-Hsp90 also showed similar level of cytotoxicity in AsPC-1, PANC-1 (Figure 2C), and MIA PaCa-2 (Figure S2B) cells, possibly because of the presence of lipoplex (and not liposome)-bound Dex, a GR synthetic ligand with known anticancer effect.…”

Section: Resultsmentioning

confidence: 99%

“…31,32 The vital heat shock protein for cancer, Hsp90, can also be selectively downregulated in tumor when targeted via expressed GR. As a result potent, antitumor activity was observed.…”

Section: Introductionmentioning

confidence: 99%

“…As a result potent, antitumor activity was observed. 32 Even using Dex-associated gold nanoparticle (Dex-GNP) we showed that GR is indeed a potential target for cancer. 33 Recently, we developed an orally administrable, anticancer drug, ESC8 that has the ability to down-regulate mTOR pathway, target breast cancer cells of all stages and induce cisplatin-sensitization in breast tumor.…”

Section: Introductionmentioning

confidence: 99%

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Glucocorticoid Receptor-Targeted Liposomal Codelivery of Lipophilic Drug and Anti-Hsp90 Gene: Strategy to Induce Drug-Sensitivity, EMT-Reversal, and Reduced Malignancy in Aggressive Tumors

et al. 2016

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Many cancers including the late stage ones become drug-resistant and undergo epithelial-to-mesenchymal transition (EMT). These lead to enhanced invasion, migration, and metastasis toward manifesting its aggressiveness and malignancy. One of the key hallmarks of cancer is its overdependence on glycolysis as its preferred energy metabolism pathway. The strict avoidance of alternate energy pathway gluconeogenesis by cancer cells points to a yet-to-be hoisted role of glucocorticoid receptor (GR) especially in tumor microenvironment, where cells are known to become drug-sensitive through induction of gluconeogenesis. However, since GR is involved in metabolism, anti-inflammatory reactions, immunity besides inducing gluconeogenesis, a greater role of GR in tumor microenvironment is envisaged. We have shown previously that GR, although ubiquitously expressed in all cells; afford to be an effective cytoplasmic target for killing cancer cells selectively. Herein, we report the therapeutic use of a newly developed GR-targeted liposomal concoction (DXE) coformulating a lipophilic drug (ESC8) and an anti-Hsp90 anticancer gene against aggressive tumor models. This induced drug-sensitivity and apoptosis while reversing EMT in tumor cells toward effective retardation of aggressive growth in pancreas and skin tumor models. Additionally, the ESC8-free lipid formulation upon cotreatment with hydrophilic drugs, gemcitabine and doxorubicin, could effectively sensitize and kill pancreatic cancer and melanoma cells, respectively. The formulation-triggered EMT-reversal was GR-dependent. Overall, we found a new strategy for drug sensitization that led to the advent of new GR-targeted anticancer therapeutics.

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Section: Resultsmentioning

confidence: 99%

“…31,32 The vital heat shock protein for cancer, Hsp90, can also be selectively downregulated in tumor when targeted via expressed GR. As a result potent, antitumor activity was observed.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glucocorticoid Receptor-Targeted Liposomal Codelivery of Lipophilic Drug and Anti-Hsp90 Gene: Strategy to Induce Drug-Sensitivity, EMT-Reversal, and Reduced Malignancy in Aggressive Tumors

et al. 2016

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“…Pore et al. prepared glucocorticoid receptor (GR)‐targeted liposomes to deliver plasmid expressing artificial miRNA against Hsp90 (amiR‐Hsp90) and showed significant anti‐tumor effect in B16F10 melanoma and A549 lung cancer in mice . Wu and coworkers have prepared cationic liposomes using DOTMA:Chol:D‐Alpha‐tocopheryl polyethylene glycol 1000 succinate (TPGS) to deliver miR‐29b to treat NSCLC.…”

Section: Nanocarriersmentioning

confidence: 96%

Organic Nanocarriers for Delivery and Targeting of Therapeutic Agents for Cancer Treatment

Peng

Bariwal

Kumar

et al. 2020

Advanced Therapeutics

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Nanocarriers have the capability to deliver a variety of drugs to disease sites. Different biological barriers prevent the successful delivery of nanoformulations to target sites, thereby limiting effective therapeutic response. Although numerous efforts have been made to design novel nanocarriers by incorporating various functionalities to get better therapies, most strategies have failed to translate drug delivery systems to the clinic. Impediments such as the incapability to hold drugs stably in nanocarriers during circulation, non‐specific distribution, and inadequate delivery of therapeutic agents to target sites due to complex tumor microenvironment remain a challenge. Herein, different organic polymer and lipid‐based nanocarriers and their encouraging therapeutic effectiveness to treat cancer are discussed. Recent development in multifunctional and stimuli sensitive nanocarriers is also highlighted. Finally, the challenges and innovative strategies to overcome various obstacles and limitations for their successful translation into the clinic are discussed.

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“…In another study, Pore et al have described new strategy for gene therapy by using glucocorticoid receptor (GR)-targeted liposome, delivering a specially designed artificial miRNA-plasmid against Hsp90 (amiR-Hsp90). Their straightforward strategy for simultaneous targeting of multiple pro-cancerous factors, have shown significant anticancer effect without eliciting nonspecific side effects on two different tumor models in mice (Pore et al 2013).…”

Section: Peptide/protein Drugsmentioning

confidence: 99%

Liposome-targeted delivery for highly potent drugs

Bardania

Tarvirdipour

Dorkoosh

2017

Artificial Cells, Nanomedicine, and Biotechnology

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Considerable adverse side effects and cytotoxicity of highly potent drugs for healthy tissue require the development of novel drug delivery systems to improve pharmacokinetics and result in selective distribution of the loaded agent. The introduction of targeted liposomal formulations has provided potential solutions for improved drug delivery to cancer cells, penetrating delivery through blood-brain barrier and gene therapy. A large number of investigations have been developed over the past few decades to overcome pharmacokinetics and unfavorable side effects limitations. These improvements have enabled targeted liposome to meet criteria for successful and improved potent drug targeting. Promising in vitro and in vivo results for liposomal-directed delivery systems appear to be effective for vast variety of highly potent therapeutics. This review will focus on the past decade's potential use and study of highly potent drugs using targeted liposomes.

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Hsp90-targeted miRNA-liposomal formulation for systemic antitumor effect

Cited by 25 publications

References 35 publications

Glucocorticoid Receptor-Targeted Liposomal Codelivery of Lipophilic Drug and Anti-Hsp90 Gene: Strategy to Induce Drug-Sensitivity, EMT-Reversal, and Reduced Malignancy in Aggressive Tumors

Glucocorticoid Receptor-Targeted Liposomal Codelivery of Lipophilic Drug and Anti-Hsp90 Gene: Strategy to Induce Drug-Sensitivity, EMT-Reversal, and Reduced Malignancy in Aggressive Tumors

Organic Nanocarriers for Delivery and Targeting of Therapeutic Agents for Cancer Treatment

Liposome-targeted delivery for highly potent drugs

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