A Freeze‐Concentration and Polyampholyte‐Modified Liposome‐Based Antigen‐Delivery System for Effective Immunotherapy

Ahmed, Sana; Fujita, Shin; Matsumura, Kazuaki

doi:10.1002/adhm.201700207

Cited by 10 publications

(6 citation statements)

References 39 publications

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“…More advanced strategies to facilitate immunogenic delivery into the cytosol depend on the lower pH of the early/late endosome . For example, CaP skeleton as a shell protects CpG oligonucleotides from clearance by macropinocytosis and responds to acidic organelle environment for on‐command release in cytosol .…”

Section: Nanomaterials For Target Deliverymentioning

confidence: 99%

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

Liu

Zhang

2019

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124

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Cancer immunotherapy is a promising cancer terminator by directing the patient's own immune system in the fight against this challenging disorder. Despite the monumental therapeutic potential of several immunotherapy strategies in clinical applications, the efficacious responses of a wide range of immunotherapeutic agents are limited in virtue of their inadequate accumulation in the tumor tissue and fatal side effects. In the last decades, increasing evidences disclose that nanotechnology acts as an appealing solution to address these technical barriers via conferring rational physicochemical properties to nanomaterials. In this Review, an imperative emphasis will be drawn from the current understanding of the effect of a nanosystem's structure characteristics (e.g., size, shape, surface charge, elasticity) and its chemical modification on its transport and biodistribution behavior. Subsequently, rapid‐moving advances of nanoparticle‐based cancer immunotherapies are summarized from traditional vaccine strategies to recent novel approaches, including delivery of immunotherapeutics (such as whole cancer cell vaccines, immune checkpoint blockade, and immunogenic cell death) and engineered immune cells, to regulate tumor microenvironment and activate cellular immunity. The future prospects may involve in the rational combination of a few immunotherapies for more efficient cancer inhibition and elimination.

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Section: Nanomaterials For Target Deliverymentioning

confidence: 99%

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

Liu

Zhang

2019

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124

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“…This is because the adsorption and internalization of proteins into the cells generally have a linear relationship, as the number of particles that adhere to the cell membrane will reflect that of particles being transferred inside the cells, as has been observed in our previous studies. 7,8,52,53 Overall, this detailed study demonstrated the efficient use of the ice-crystal-based freezing approach to the internalization of proteins with the help of a unique polyampholyte cryoprotectant.…”

Section: ■ Discussionmentioning

confidence: 99%

Enhanced Adsorption of a Protein–Nanocarrier Complex onto Cell Membranes through a High Freeze Concentration by a Polyampholyte Cryoprotectant

2018

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The transportation of biomolecules into cells is of great importance in tissue engineering and as stimulation for antitumor immune cells. Previous freezing strategies at ultracold temperatures (-80 °C) used for intracellular transportation exhibit certain limitations such as extended time requirements and harsh delivery system conditions. Thus, the need remains to develop simplified methods for safe nanomaterial delivery. Here, we demonstrated a unique strategy based on the ice-crystallization-induced freeze concentration for protein intracellular delivery in combination with a polyampholyte cryoprotectant. We found that upon sustained lowering of the temperature from -6 to -20 °C over a short duration, the adsorption of proteins onto the peripheral cell membrane was markedly increased through the facile ice-crystallization-induced freeze concentration. Furthermore, we proposed a freeze concentration factor (α) that depends on the freezing-point depression and is estimated from an analysis of the fraction of frozen water. Notably, the α values of the polyampholyte cryoprotectant were 8-fold higher than those of the currently used cryoprotectant dimethyl sulfoxide (DMSO) at particular temperatures of interest. Our results illustrate that the presence of a polyampholyte cryoprotectant significantly enhanced the adsorption of the protein/nanocarrier complex onto membranes compared to that obtained with DMSO because of the high freeze concentration. The present study demonstrated the direct relationship between freezing and the penetration of proteins across the periphery of the cell membrane by means of increased concentration during freezing. These results may be useful in providing a guideline for the intracellular delivery of biomacromolecules using ice-crystallization-induced continuous freezing combined with polyampholyte cryoprotectants.

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“…The release of OVA from MRPRPNs and PRPNs was determined by analyzing the florescence intensity of pyramine as reported in previous studies [34,[47][48][49]. Briefly, pyramine (50 mL)-loaded MRPRPNs were dispersed in different pH buffers, i.e.…”

Section: Ova Content Determination (% Ee)mentioning

confidence: 99%

Release promoter-based systematically designed nanocomposite(s): a novel approach for site-specific delivery of tumor-associated antigen(s) (TAAs)

Sharma

Dubey

Mody

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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The aim of present approach was to design and develop mannose functionalized reverse polymeric nanocomposite(s) system based on release promoter (MRPRPNs). Thus, the composition of the present formulation was optimized by employing the systematic design of experiments (DoE) for screening and optimization using L8-Array Taguchi and 3-level-3-factor Box-Behnken Design (BBD). Further, the developed formulation was observed for its preferential internalization by professional antigen presenting cells (macrophages/dendritic cells) and prompt release of loaded antigen in a pH-dependent manner. The optimized formulation was also extensively characterized for average hydrodynamic diameter, surface potential, poly dispersity index of reverse polymeric nanocomposite(s) which were recoded to be 189.4 ± 8.52 nm, 0.111 ± 0.024, -23.4 ± 2.0 mV, respectively; while percentage entrapment efficiency of OVA in MRPRPNs to be 60.17 ± 2.41%. The release pattern of OVA from MRPRPNs was consistent at pH 7.4. However, at acidic pH (≈5.5) where in protons (H) are in-filtered into the core of MRPRPNs thereby generating the pressure, resultantly causing and creating the pores or disruption of the system thus allowed a prompt release (≈60-70%) of encapsulated OVA from interior to outer milieu within 1 h. MRPRPNs were preferentially internalized through receptor-mediated endocytosis and released the loaded OVA into the cytosol of RAW 264.7 cells. From the above findings, it can be concluded that reverse polymeric system could significantly be loaded with immunobioactive(s) and could potentially deliver the contents at the specific site for the better therapeutic outcome.

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A Freeze‐Concentration and Polyampholyte‐Modified Liposome‐Based Antigen‐Delivery System for Effective Immunotherapy

Cited by 10 publications

References 39 publications

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

Enhanced Adsorption of a Protein–Nanocarrier Complex onto Cell Membranes through a High Freeze Concentration by a Polyampholyte Cryoprotectant

Release promoter-based systematically designed nanocomposite(s): a novel approach for site-specific delivery of tumor-associated antigen(s) (TAAs)

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