Single Micelle Vectors based on Lipid/Block Copolymer Compositions as mRNA Formulations for Efficient Cancer Immunogene Therapy

Li, Jingmei; Men, Ke; Jin, Wu; Lei, Sibei; Yang, Yang; Pan, Haixia

doi:10.1021/acs.molpharmaceut.1c00461

Cited by 20 publications

(20 citation statements)

References 53 publications

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“…In this study, we prepared a single vector named DMP. As DMP has been used for systemic administration in animal models several times, 25,41 we attempted to use it as a delivery vector for OSCC suicide gene therapy. We evaluated the protection quality, safety, distribution, and metabolism in mouse models of DMP.…”

Section: Discussionmentioning

confidence: 99%

Local and Systemic Delivery of the BimS Gene Nano-Complex for Efficient Oral Squamous Cell Carcinoma Therapy

Ma¹,

Li²,

Jin³

et al. 2022

IJN

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Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, with more than 300,000 new cases annually. Despite advances in existing treatments, including surgery, radiation, chemotherapy, and immunotherapy, the overall survival and prognosis have remained poor. However, gene therapy based on non-viral vectors provides new ideas for the treatment of OSCC. Here, we aimed to prepare and describe the synthesis, biosafety, and preclinical efficacy of DOTAP-mPEG-PCL (DMP) in OSCC gene therapy. Methods: We prepared a nano-sized hybrid cationic micelle DMP. DMP micelles were prepared by self-assembling cationic lipid DOTAP and mPEG-PCL polymer. We evaluated the characteristics of this cationic micelle in vitro. Combined with encoding the apoptosis-inducing BimS gene, we established the DMP/phBimS complex and evaluated its anti-tumor effect in vitro. We also established a mouse tongue xenograft model to evaluate the antitumor effect of the DMP/phBimS complex in vivo through local and systemic administration prospectively. Results:The DMP cationic micelle is spherical in shape, with an average diameter of 28.32 ± 3.56 nm and an average zeta potential of 43.43 ± 0.82 mV. By activation of lipid raft-mediated endocytosis caveolin-mediated endocytosis, DMP could efficiently deliver plasmid into SCC15 cells (efficiency: 52.07% ± 1.63%), with an ideal biosecurity. When loaded by plasmid encoding the apoptosisinducing BimS gene, the DMP/phBimS complex exhibited an obvious anti-proliferation effect of SCC15 in vitro through the apoptosis pathway (33.9% ± 2.62% apoptosis rate). By local administration, the DMP/phBimS complex showed ideal anti-tumor properties in the nude mouse tongue xenograft model, with an average tumor inhibition rate of 65.66%. Furthermore, through systematic administration, the DMP/phBimS complex obviously inhibited OSCC growth, with an average inhibition rate of 45.63% (DMP/ phBimS) and an appropriate biocompatibility. Conclusion:The DMP/phBimS complex is an optional effective option for suicide gene therapy for OSCC.

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Section: Discussionmentioning

confidence: 99%

Local and Systemic Delivery of the BimS Gene Nano-Complex for Efficient Oral Squamous Cell Carcinoma Therapy

Ma¹,

Li²,

Jin³

et al. 2022

IJN

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“…Nanoparticle Preparation: DMP was a self-assembled nanoparticle, and DMP-HCC167 was synthesized by linking the polypeptide HCC167 to DMP. [30] First, N- [1-(2,3-dioleoyloxy) propyl]-N, N,N-trimethylammonium methyl-sulfate (DOTAP, Avanti) and the mPEG-PCL polymer (Ruixibio, China) (1:9, w/w) were dissolved in dichloromethane. After 45 min of rotary evaporation of the polymer solution with a rotary evaporator, milli-Q water was added to the distillation flask for hydration.…”

Section: Methodsmentioning

confidence: 99%

ALPPL2‐Binding Peptide Facilitates Targeted mRNA Delivery for Efficient Hepatocellular Carcinoma Gene Therapy

Lei

Chen

Ming

et al. 2022

Adv Funct Materials

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mRNA-based gene therapy has emerged as an advanced strategy for hepatocellular carcinoma (HCC) treatment. However, one of its main limitations is lacking delivery precision in vivo. Distinguishing HCC cells from other tissues is crucial for maintaining the high stability, positive therapeutic outcomes, and safety of mRNA therapeutics. Here, a novel HCC specific peptide HCC167 is developed by phage display. It is shown that the HCC167 peptide can specifically recognize variety of HCC substrates including patient samples with high affinity. Modifying nanoparticles with the HCC167 peptide facilitates an effective HCC active targeting ability. When loading with Bims-encoding mRNA, the systemically administrated DMP-HCC167/Bims complex efficiently suppresses HCC progression in multiple models including patient-derived xenografts. Furthermore, the ALPPL2 protein is identified as a specific binding receptor of the HCC167 peptide on the HCC cell membrane, uncovering a new active targeting mechanism based on the HCC167-ALPPL2 ligand-receptor complex. The binding structure is also investigated by computer-aided modeling. The study hence exhibits a potent active targeting strategy for mRNA-based HCC therapy.

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“…The self-assembly of amphiphilic polymers into micelles makes them excellent gene carriers. Amphiphilic cationic polymers such as polylysine (PLL) [96], PEI [97,98], polyamidoamine (PAMAM) [99], and polydimethylaminoethyl methacrylate (PDMAEMA) [100,101] are commonly used to construct cationic micelles [102,103].…”

Section: Micellesmentioning

confidence: 99%

Nonviral delivery systems for antisense oligonucleotide therapeutics

Huang

Hao

et al. 2022

Biomater Res

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Antisense oligonucleotides (ASOs) are an important tool for the treatment of many genetic disorders. However, similar to other gene drugs, vectors are often required to protect them from degradation and clearance, and to accomplish their transport in vivo. Compared with viral vectors, artificial nonviral nanoparticles have a variety of design, synthesis, and formulation possibilities that can be selected to accomplish protection and delivery for specific applications, and they have served critical therapeutic purposes in animal model research and clinical applications, allowing safe and efficient gene delivery processes into the target cells. We believe that as new ASO drugs develop, the exploration for corresponding nonviral vectors is inevitable. Intensive development of nonviral vectors with improved delivery strategies based on specific targets can continue to expand the value of ASO therapeutic approaches. Here, we provide an overview of current nonviral delivery strategies, including ASOs modifications, action mechanisms, and multi-carrier methods, which aim to address the irreplaceable role of nonviral vectors in the progressive development of ASOs delivery.

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Single Micelle Vectors based on Lipid/Block Copolymer Compositions as mRNA Formulations for Efficient Cancer Immunogene Therapy

Cited by 20 publications

References 53 publications

Local and Systemic Delivery of the BimS Gene Nano-Complex for Efficient Oral Squamous Cell Carcinoma Therapy

Local and Systemic Delivery of the BimS Gene Nano-Complex for Efficient Oral Squamous Cell Carcinoma Therapy

ALPPL2‐Binding Peptide Facilitates Targeted mRNA Delivery for Efficient Hepatocellular Carcinoma Gene Therapy

Nonviral delivery systems for antisense oligonucleotide therapeutics

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