Chemically Designed Functional Nanomicelles for Blood–Brain Barrier Crossing

Ankan Kumar Sarkar; Sudipta Jana; Guneet Kaur; Himali Arora; Sourav Barman; Nayana Mukherjee; Santanu Shaw; Amit Ranjan Maity; Pankaj Seth; Nihar R. Jana; Nikhil R. Jana

doi:10.1021/acs.nanolett.5c03705

Chemically Designed Functional Nanomicelles for Blood–Brain Barrier Crossing

Ankan Kumar Sarkar, Sudipta Jana, Guneet Kaur, Himali Arora, Sourav Barman, Nayana Mukherjee, Santanu Shaw, Amit Ranjan Maity, Pankaj Seth, Nihar R. Jana, Nikhil R. Jana

Research output: Contribution to journal › Letter › peer-review

Abstract

The blood–brain barrier (BBB) is a specialized semipermeable structure that restricts the exchange of materials between central nervous system parenchyma and blood vessels. Nanocarriers have shown the potential to cross the BBB via receptor-mediated transcytosis (RMT) or adsorption-mediated transcytosis (AMT), though efficiency remains limited. Here, we report two different polymer nanomicelles of 20–60 nm size that efficiently cross the BBB via either RMT or AMT. We have tested their performance in a transwell-based model, tumor spheroid model, and in vivo mice model. We found that lower numbers of receptors per nanomicelle are critical for RMT and direct membrane penetration property of nanomicelle is critical for AMT. Transcytosis can be enhanced by 8–10 times using the optimized nanomicelles that leads to 8 times enhanced penetration in tumor spheroid and 26–35 times enhanced delivery to deep brain tissue. These polymer nanomicelles can be used as nanocarrier for in vivo delivery of therapeutic biomolecules in brain.

Original language	English
Pages (from-to)	15550-15556
Number of pages	7
Journal	Nano Letters
Volume	25
Issue number	43
DOIs	https://doi.org/10.1021/acs.nanolett.5c03705
State	Published - 29 Oct 2025
Externally published	Yes

Keywords

blood−brain barrier
guanidinium
nanodrug
nanoparticle
polymer micelle
transcytosis
transferrin
tumor spheroid

ASJC Scopus subject areas

Bioengineering
General Chemistry
General Materials Science
Condensed Matter Physics
Mechanical Engineering

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10.1021/acs.nanolett.5c03705

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title = "Chemically Designed Functional Nanomicelles for Blood–Brain Barrier Crossing",

abstract = "The blood–brain barrier (BBB) is a specialized semipermeable structure that restricts the exchange of materials between central nervous system parenchyma and blood vessels. Nanocarriers have shown the potential to cross the BBB via receptor-mediated transcytosis (RMT) or adsorption-mediated transcytosis (AMT), though efficiency remains limited. Here, we report two different polymer nanomicelles of 20–60 nm size that efficiently cross the BBB via either RMT or AMT. We have tested their performance in a transwell-based model, tumor spheroid model, and in vivo mice model. We found that lower numbers of receptors per nanomicelle are critical for RMT and direct membrane penetration property of nanomicelle is critical for AMT. Transcytosis can be enhanced by 8–10 times using the optimized nanomicelles that leads to 8 times enhanced penetration in tumor spheroid and 26–35 times enhanced delivery to deep brain tissue. These polymer nanomicelles can be used as nanocarrier for in vivo delivery of therapeutic biomolecules in brain.",

keywords = "blood−brain barrier, guanidinium, nanodrug, nanoparticle, polymer micelle, transcytosis, transferrin, tumor spheroid",

author = "Sarkar, \{Ankan Kumar\} and Sudipta Jana and Guneet Kaur and Himali Arora and Sourav Barman and Nayana Mukherjee and Santanu Shaw and Maity, \{Amit Ranjan\} and Pankaj Seth and Jana, \{Nihar R.\} and Jana, \{Nikhil R.\}",

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year = "2025",

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doi = "10.1021/acs.nanolett.5c03705",

language = "English",

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T1 - Chemically Designed Functional Nanomicelles for Blood–Brain Barrier Crossing

AU - Sarkar, Ankan Kumar

AU - Jana, Sudipta

AU - Kaur, Guneet

AU - Arora, Himali

AU - Barman, Sourav

AU - Mukherjee, Nayana

AU - Shaw, Santanu

AU - Maity, Amit Ranjan

AU - Seth, Pankaj

AU - Jana, Nihar R.

AU - Jana, Nikhil R.

PY - 2025/10/29

Y1 - 2025/10/29

N2 - The blood–brain barrier (BBB) is a specialized semipermeable structure that restricts the exchange of materials between central nervous system parenchyma and blood vessels. Nanocarriers have shown the potential to cross the BBB via receptor-mediated transcytosis (RMT) or adsorption-mediated transcytosis (AMT), though efficiency remains limited. Here, we report two different polymer nanomicelles of 20–60 nm size that efficiently cross the BBB via either RMT or AMT. We have tested their performance in a transwell-based model, tumor spheroid model, and in vivo mice model. We found that lower numbers of receptors per nanomicelle are critical for RMT and direct membrane penetration property of nanomicelle is critical for AMT. Transcytosis can be enhanced by 8–10 times using the optimized nanomicelles that leads to 8 times enhanced penetration in tumor spheroid and 26–35 times enhanced delivery to deep brain tissue. These polymer nanomicelles can be used as nanocarrier for in vivo delivery of therapeutic biomolecules in brain.

AB - The blood–brain barrier (BBB) is a specialized semipermeable structure that restricts the exchange of materials between central nervous system parenchyma and blood vessels. Nanocarriers have shown the potential to cross the BBB via receptor-mediated transcytosis (RMT) or adsorption-mediated transcytosis (AMT), though efficiency remains limited. Here, we report two different polymer nanomicelles of 20–60 nm size that efficiently cross the BBB via either RMT or AMT. We have tested their performance in a transwell-based model, tumor spheroid model, and in vivo mice model. We found that lower numbers of receptors per nanomicelle are critical for RMT and direct membrane penetration property of nanomicelle is critical for AMT. Transcytosis can be enhanced by 8–10 times using the optimized nanomicelles that leads to 8 times enhanced penetration in tumor spheroid and 26–35 times enhanced delivery to deep brain tissue. These polymer nanomicelles can be used as nanocarrier for in vivo delivery of therapeutic biomolecules in brain.

KW - blood−brain barrier

KW - guanidinium

KW - nanodrug

KW - nanoparticle

KW - polymer micelle

KW - transcytosis

KW - transferrin

KW - tumor spheroid

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U2 - 10.1021/acs.nanolett.5c03705

DO - 10.1021/acs.nanolett.5c03705

M3 - Letter

C2 - 41099381

AN - SCOPUS:105020206133

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SP - 15550

EP - 15556

JO - Nano Letters

JF - Nano Letters

IS - 43

ER -

Chemically Designed Functional Nanomicelles for Blood–Brain Barrier Crossing

Abstract

Keywords

ASJC Scopus subject areas

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