A novel cationic lipid with intrinsic antitumor activity to facilitate gene therapy of TRAIL DNA

Luo, Cong; Miao, Lei; Zhao, Yi; Musetti, Sara; Wang, Yuhua; Shi, Kai; Huang, Leaf

doi:10.1016/j.biomaterials.2016.06.030

Cited by 62 publications

(40 citation statements)

References 22 publications

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“…VEGF and Bcl-2) [71]. Based on this, metformin has been further exploited to conjugate with hydrophobic lipid chains to form cationic lipid-like drugs, and thus co-encapsulating siRNA or DNA for combinatory or synergistic purposes [135, 140] (Figure 4). …”

Section: Combination Of Sirna/chemodrugs In a Single Carriermentioning

confidence: 99%

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Nanoformulations for combination or cascade anticancer therapy

Miao

Guo

Lin

et al. 2017

Advanced Drug Delivery Reviews

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146

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Nanoparticle drug formulations have been extensively investigated, developed, and in some cases, approved by the Food and Drug Administration (FDA). Synergistic combinations of drugs having distinct tumor-inhibiting mechanisms and non-overlapping toxicity can circumvent the issue of treatment resistance and may be essential for effective anti-cancer therapy. At the same time, co-delivery of a combined regimen by a single nanocarrier presents a challenge due to differences in solubility, molecular weight, functional groups and encapsulation conditions between the two drugs. This review discusses cellular and microenvironment mechanisms behind treatment resistance and nanotechnology-based solutions for effective anti-cancer therapy. Co-loading or cascade delivery of multiple drugs using of polymeric nanoparticles, polymer-drug conjugates and lipid nanoparticles will be discussed along with lipid-coated drug nanoparticles developed by our lab and perspectives on combination therapy.

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Section: Combination Of Sirna/chemodrugs In a Single Carriermentioning

confidence: 99%

“…D. Schematic illustration of LPD-TRAIL NPs using metformin-lipid as a carrier for gene delivery. Copyright of 2016 Nature group [71] and Elsevier [140]. …”

Section: Figurementioning

confidence: 99%

Nanoformulations for combination or cascade anticancer therapy

Miao

Guo

Lin

et al. 2017

Advanced Drug Delivery Reviews

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146

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“…These findings confirmed that NPs had no observable toxicities on normal tissues despite their cationic charge, which can most likely be attributed to the PEG shielding effect of the PEGylated NPs. Additionally, a recently published manuscript found that PEGylated DOTAP particles with similar surface charges and NP structure, had low toxicity on normal lung fibroblasts MRC-5, further confirming the minimal toxicity properties of the blank NPs [26]. …”

Section: Resultsmentioning

confidence: 75%

Co-delivery of polymeric metformin and cisplatin by self-assembled core-membrane nanoparticles to treat non-small cell lung cancer

Xiong

Zhao

Miao

et al. 2016

Journal of Controlled Release

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Clinically, combined therapy of cisplatin (CDDP) and metformin is an effective treatment for non-small cell lung cancer (NSCLC). The success is attributed to synergistic effects between the two drugs. Therefore, we hypothesize that co-encapsulation of CDDP and metformin will avoid the prominent toxicity of CDDP while maintaining the synergy between the regimens. CDDP was first conjugated to polyglutamic acid (PGA) to form anionic PGA-CDDP which was electrostatically complexed with the cationic polymeric metformin (polymet). The nano-sized complex was then stabilized with cationic liposomes composed of DOTAP (2, 3-Dioleoyloxy-propyl)-trimethylammonium/Cholesterol/DSPE-PEG-anisamide aminoethyl. Both in vitro and in vivo experiments confirmed the synergy between polymet and CDDP. CDDP delivered with nanoparticles (NPs) exhibited significantly increased tumor accumulation over free CDDP and suppressed tumor growth through apoptosis in NSCLC H460 tumor-bearing mice without nephrotoxicity. The synergistic effect of polymet alongside CDDP demonstrates that polymet-CDDP NPs can activate the AMP-activated protein kinase α (AMPKα) pathway and inhibit mammalian target rapamycin (mTOR) activity to enhance growth suppression. In all, this platform is the first to successfully co-load polymet, a polymeric metformin, and CDDP into the same nanoparticle for successful treatment of NSCLC.

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“…Another important commonly studied gene is TRAIL, which encodes a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein induces apoptosis preferentially in cancer cells (14)(15). Other genes members of the TNF-receptor family expressed in normal apoptosis process are FAS (encodes induced cellular death), FASL (encodes a membrane protein for the induction of apoptosis), and BCL2 (encodes a membrane receptor for tumor necrosis factor α) (14,16).…”

Section: Death-induced Gene Therapymentioning

confidence: 99%

Nanoparticles for death‑induced gene therapy in cancer (Review)

et al. 2017

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Due to the high toxicity and side effects of the use of traditional chemotherapy in cancer, scientists are working on the development of alternative therapeutic technologies. An example of this is the use of death‑induced gene therapy. This therapy consists of the killing of tumor cells via transfection with plasmid DNA (pDNA) that contains a gene which produces a protein that results in the apoptosis of cancerous cells. The cell death is caused by the direct activation of apoptosis (apoptosis‑induced gene therapy) or by the protein toxic effects (toxin‑induced gene therapy). The introduction of pDNA into the tumor cells has been a challenge for the development of this therapy. The most recent implementation of gene vectors is the use of polymeric or inorganic nanoparticles, which have biological and physicochemical properties (shape, size, surface charge, water interaction and biodegradation rate) that allow them to carry the pDNA into the tumor cell. Furthermore, nanoparticles may be functionalized with specific molecules for the recognition of molecular markers on the surface of tumor cells. The binding between the nanoparticle and the tumor cell induces specific endocytosis, avoiding toxicity in healthy cells. Currently, there are no clinical protocols approved for the use of nanoparticles in death‑induced gene therapy. There are still various challenges in the design of the perfect transfection vector, however nanoparticles have been demonstrated to be a suitable candidate. This review describes the role of nanoparticles used for pDNA transfection and key aspects for their use in death‑induced gene therapy.

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A novel cationic lipid with intrinsic antitumor activity to facilitate gene therapy of TRAIL DNA

Cited by 62 publications

References 22 publications

Nanoformulations for combination or cascade anticancer therapy

Nanoformulations for combination or cascade anticancer therapy

Co-delivery of polymeric metformin and cisplatin by self-assembled core-membrane nanoparticles to treat non-small cell lung cancer

Nanoparticles for death‑induced gene therapy in cancer (Review)

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