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Highly Stable Fluorinated Nanocarriers with iRGD for Overcoming the Stability Dilemma and Enhancing Tumor Penetration in an Orthotopic Breast Cancer
Abstract
The stability dilemma and limited tumor penetration of nanocarriers in cancer chemotherapy remain two predominant challenges for their successful clinical translation. Herein, the pH-sensitive fluorocarbon-functionalized nanocarriers (SFNs) with a tumor-homing and penetrating peptide iRGD are reported to overcome the stability dilemma and enhance tumor accumulation and penetration in an orthotopic breast cancer. The highly stable SFNs with a low critical association concentration provide a safe and spacious harbor for hydrophobic drugs. Furthermore, the stimulus-responsive evaluation and <i>in vitro</i> drug release study show that the SFNs can balance intracellular dissociation for drug release and extracellular stability in the blood circulation. Additionally, the tumor penetration capacity has been dramatically enhanced in 3D multicellular spheroids, effectively affecting cells far from the periphery. This can be ascribed to the coadministration of iRGD having tumor-penetrating ability and fluorocarbon chains having good cell membrane permeability. The combination of SFNs and iRGD is a viable approach to assist drugs’ effective accumulation in primary and metastasized tumor sites, significantly inhibiting the breast tumor growth and curbing lung and liver metastases in an orthotopic-tumor-bearing mouse model. Taken together, this pH-sensitive fluorinated nanosystem having excellent stability and tumor accumulation and penetration properties paves the way to combat cancer- Text
- Journal contribution
- Medicine
- Cell Biology
- Pharmacology
- Biotechnology
- Cancer
- Space Science
- Biological Sciences not elsewhere classified
- Information Systems not elsewhere classified
- metastasized tumor sites
- breast tumor growth
- drug release study show
- orthotopic breast cancer
- SFN
- 3 D multicellular spheroids
- tumor accumulation
- cell membrane permeability
- pH-sensitive fluorocarbon-functionalized nanocarriers
- Stable Fluorinated Nanocarriers
- iRGD
- Orthotopic Breast Cancer
- tumor penetration capacity
- Enhancing Tumor Penetration
- stability dilemma
- orthotopic-tumor-bearing mouse model