Enhanced delivery of lipid nanoparticle-based immunotherapy by modulating the tumor tissue stiffness using ultrasound-activated nanobubbles DOI

Anubhuti Bhalotia,

Pinunta Nittayacharn, Meghna Mehta

et al.

Published: April 19, 2025

Abstract Tumors often exhibit an extracellular matrix with elevated stiffness due to excessive accumulation and crosslinking of proteins, particularly collagen. This acts as a physical barrier, impeding the infiltration immune cells effective delivery various immunotherapeutic agents, such lipid nanoparticle-based RNA therapeutics. Here, we investigate ability ultrasound-activated nanobubbles (US-NBs) increase permeability immunogenicity tumors. Our results show that US-NBs physically remodel tumor tissue by decreasing its 60% five days after single treatment. US-NB-treated tumors display randomly oriented collagen 5.47-fold lower deposition compared untreated leads widespread distribution nanoparticles (LNPs) in tumor. When LNPs are assisted US-NB, they have higher gene-transfection across pan-immune relative alone. Notably, US-NB enables genetically modify T directly vivo. By effectively engaging both arms system, US-NB-assisted enhance cytotoxic 4-fold when These indicate gentle mechanical stimulation using offers promising strategy augment efficacy existing immunotherapies. Graphical

Language: Английский

Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and their targeting in cancer therapy DOI Creative Commons

Shuyan He,

Lu Zheng,

Chunjian Qi

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 8, 2025

Language: Английский

Citations

2
Lipid Nanoparticles and PEG: Time Frame of Immune Checkpoint Blockade Can Be Controlled by Adjusting the Rate of Cellular Uptake of Nanoparticles DOI

Andrew S. Choi,

Taylor J. Moon,

Anubhuti Bhalotia

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

The engineerability of lipid nanoparticles (LNPs) and their ability to deliver nucleic acids make LNPs attractive tools for cancer immunotherapy. LNP-based gene delivery can be employed various approaches in immunotherapy, including encoding tumor-associated antigens silencing negative immune checkpoint proteins. For example, carrying small interfering RNAs offer several advantages, sustained durable inhibition an protein. Due tunable design, modifying the composition regulate rate uptake by cells silencing. Controlling kinetics LNP provides additional flexibility strategies generate appropriate immunomodulation tumor microenvironment. Here, we evaluated effects polyethylene glycol (PEG) content ranging from 0.5 6 mol % on cellular PD-L1 after intratumoral administration. We blockade vitro cell studies vivo using YUMM1.7 melanoma model. Cell showed that was inversely correlated increasing PEG a linear relationship. In studies, 0.5% initiated immediate effect with significant decrease expression observed within 24 h. comparison, 6% delayed, subsets being 72 h Notably, performance at comparable Overall, this study suggests modifications administration promising strategy effective antitumor response.

Language: Английский

Citations

0
Enhanced delivery of lipid nanoparticle-based immunotherapy by modulating the tumor tissue stiffness using ultrasound-activated nanobubbles DOI

Anubhuti Bhalotia,

Pinunta Nittayacharn, Meghna Mehta

et al.

Published: April 19, 2025

Abstract Tumors often exhibit an extracellular matrix with elevated stiffness due to excessive accumulation and crosslinking of proteins, particularly collagen. This acts as a physical barrier, impeding the infiltration immune cells effective delivery various immunotherapeutic agents, such lipid nanoparticle-based RNA therapeutics. Here, we investigate ability ultrasound-activated nanobubbles (US-NBs) increase permeability immunogenicity tumors. Our results show that US-NBs physically remodel tumor tissue by decreasing its 60% five days after single treatment. US-NB-treated tumors display randomly oriented collagen 5.47-fold lower deposition compared untreated leads widespread distribution nanoparticles (LNPs) in tumor. When LNPs are assisted US-NB, they have higher gene-transfection across pan-immune relative alone. Notably, US-NB enables genetically modify T directly vivo. By effectively engaging both arms system, US-NB-assisted enhance cytotoxic 4-fold when These indicate gentle mechanical stimulation using offers promising strategy augment efficacy existing immunotherapies. Graphical

Language: Английский

Citations

0