Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression

Nagaprasad Puvvada, Shashi Rajput, B. Prashanth Kumar, Siddik Sarkar, Suraj Konar, Keith R. Brunt, Raj R. Rao, Abhijit Mazumdar, Swadesh K. Das, Ranadhir Basu, Paul B. Fisher, Mahitosh Mandal, Amita Pathak

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ∼75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence-switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues.

Original languageEnglish (US)
Article number11760
JournalScientific reports
Volume5
DOIs
StatePublished - Jul 6 2015

Fingerprint

Paclitaxel
Folic Acid
Breast Neoplasms
Fluorescence
Neoplasms
Click Chemistry
X-Rays
Drug Therapy

All Science Journal Classification (ASJC) codes

  • General

Cite this

Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression. / Puvvada, Nagaprasad; Rajput, Shashi; Prashanth Kumar, B.; Sarkar, Siddik; Konar, Suraj; Brunt, Keith R.; Rao, Raj R.; Mazumdar, Abhijit; Das, Swadesh K.; Basu, Ranadhir; Fisher, Paul B.; Mandal, Mahitosh; Pathak, Amita.

In: Scientific reports, Vol. 5, 11760, 06.07.2015.

Research output: Contribution to journalArticle

Puvvada, Nagaprasad ; Rajput, Shashi ; Prashanth Kumar, B. ; Sarkar, Siddik ; Konar, Suraj ; Brunt, Keith R. ; Rao, Raj R. ; Mazumdar, Abhijit ; Das, Swadesh K. ; Basu, Ranadhir ; Fisher, Paul B. ; Mandal, Mahitosh ; Pathak, Amita. / Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression. In: Scientific reports. 2015 ; Vol. 5.
@article{0cbeac6f52eb41b5b470de853150f95b,
title = "Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression",
abstract = "Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ∼75{\%} of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence-switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues.",
author = "Nagaprasad Puvvada and Shashi Rajput and {Prashanth Kumar}, B. and Siddik Sarkar and Suraj Konar and Brunt, {Keith R.} and Rao, {Raj R.} and Abhijit Mazumdar and Das, {Swadesh K.} and Ranadhir Basu and Fisher, {Paul B.} and Mahitosh Mandal and Amita Pathak",
year = "2015",
month = "7",
day = "6",
doi = "10.1038/srep11760",
language = "English (US)",
volume = "5",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression

AU - Puvvada, Nagaprasad

AU - Rajput, Shashi

AU - Prashanth Kumar, B.

AU - Sarkar, Siddik

AU - Konar, Suraj

AU - Brunt, Keith R.

AU - Rao, Raj R.

AU - Mazumdar, Abhijit

AU - Das, Swadesh K.

AU - Basu, Ranadhir

AU - Fisher, Paul B.

AU - Mandal, Mahitosh

AU - Pathak, Amita

PY - 2015/7/6

Y1 - 2015/7/6

N2 - Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ∼75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence-switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues.

AB - Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ∼75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence-switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues.

UR - http://www.scopus.com/inward/record.url?scp=84936805332&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84936805332&partnerID=8YFLogxK

U2 - 10.1038/srep11760

DO - 10.1038/srep11760

M3 - Article

C2 - 26145450

AN - SCOPUS:84936805332

VL - 5

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 11760

ER -