Reversibly Stabilized Polycation Nanoparticles for Combination Treatment of Early- and Late-Stage Metastatic Breast

Related Experiment Video

Updated: Feb 8, 2026

Monitoring Breast Cancer Growth and Metastatic Colony Formation in Mice using Bioluminescence
06:52

Monitoring Breast Cancer Growth and Metastatic Colony Formation in Mice using Bioluminescence

Published on: November 5, 2021

3.7K

Gang Chen1, Yixin Wang1, Pengkai Wu1

  • 1State Key Laboratory of Natural Medicines, Department of Pharmaceutics , China Pharmaceutical University , Nanjing 210009 , China.

ACS Nano
|July 10, 2018
PubMed

Insights

New nanomedicine effectively targets both STAT3 and CXCR4 pathways, significantly inhibiting metastatic breast cancer growth and spread. This combined approach shows promise for treating advanced breast cancer with improved tumor accumulation and delivery.

Area of Science:

  • Oncology
  • Nanomedicine
  • Molecular Biology

Background:

  • Metastatic breast cancer is a leading cause of cancer mortality in women globally.
  • Signal transducer and activator of transcription 3 (STAT3) and chemokine receptor CXCR4 are key drivers of breast cancer metastasis.
  • Targeting these pathways offers a potential therapeutic strategy.

Purpose of the Study:

  • To develop a novel nanomedicine for combined inhibition of STAT3 and CXCR4 in metastatic breast cancer.
  • To synthesize and characterize CXCR4-inhibiting polymers for systemic siRNA delivery to silence STAT3.
  • To evaluate the therapeutic efficacy and mechanism of action of the developed nanomedicine.

Main Methods:

  • Synthesis of PEGylated, fluorinated, and bioreducible polymers for polyplex formation with siRNA.
  • In vivo structure-activity relationship studies in a lung metastasis model.
  • In vitro cancer cell invasion assays.
  • Pharmacokinetic analysis and biodistribution studies.
  • Assessment of therapeutic efficacy in early-stage and late-stage metastatic breast cancer models.

Main Results:

  • Bioreducible fluorinated polyplexes demonstrated superior antimetastatic activity compared to nonreducible controls.
  • Improved siRNA delivery, physical stability, serum stability, and intracellular trafficking were observed with bioreducible fluorinated polyplexes.
  • Fluorination enhanced polyplex accumulation in tumors by reducing renal clearance.
  • Combined STAT3 and CXCR4 inhibition led to significant primary tumor growth inhibition and pronounced antimetastatic effects in both tested models.
  • Mechanistic studies indicated a multifaceted mechanism involving both local and systemic effects.

Conclusions:

  • Developed bioreducible, fluorinated polyplexes effectively deliver STAT3 siRNA for combined STAT3 and CXCR4 inhibition.
  • This nanomedicine approach shows significant therapeutic potential against metastatic breast cancer.
  • The findings support further investigation of this dual-targeting strategy for clinical translation.
Keywords:
CXCR4STAT3breast cancerfluorinationmetastasissiRNA delivery

More Related Videos

Generating a Murine Orthotopic Metastatic Breast Cancer Model and Performing Murine Radical Mastectomy05:05

Generating a Murine Orthotopic Metastatic Breast Cancer Model and Performing Murine Radical Mastectomy

Published on: November 29, 2018

11.7K
Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer07:13

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer

Published on: March 26, 2014

24.0K

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.8K
Nuclear Stability03:18

Nuclear Stability

Protons and neutrons, collectively called nucleons, are packed together tightly in a nucleus. With a radius of about 10−15 meters, a nucleus is quite small compared to the radius of the entire atom, which is about 10−10 meters. Nuclei are extremely dense compared to bulk matter, averaging 1.8 × 1014 grams per cubic centimeter. If the earth’s density were equal to the average nuclear density, the earth’s radius would be only about 200 meters.
To hold positively charged protons together...
23.3K
RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
35.8K
Stability01:28

Stability

The time response of a linear time-invariant (LTI) system can be divided into transient and steady-state responses. The transient response represents the system's initial reaction to a change in input and diminishes to zero over time. In contrast, the steady-state response is the behavior that persists after the transient effects have faded.
The stability of an LTI system is determined by the roots of its characteristic equation, known as poles. A system is stable if it produces a bounded...
421
Stages of Infection01:26

Stages of Infection

Stages of infection describe what happens to a susceptible host once a pathogen invades the human body. The stages of infection are incubation, prodromal, illness, stage of decline, and convalescence. The incubation stage is the period from exposure to a pathogen until symptoms start. The infected person is unaware of impending illness as the pathogens grow and multiply within the body. The duration may vary depending on the type of infection. The incubation period of measles averages ten to...
65.3K
Reversible and Irreversible Processes01:14

Reversible and Irreversible Processes

The thermodynamic processes can be classified into reversible and irreversible processes. The processes that can be restored to their initial state are called reversible processes. It is only possible if the process is in quasi-static equilibrium, i.e., it takes place in infinitesimally small steps, and the system remains at equilibrium However, these are ideal processes and do not occur naturally. An ideal system undergoing a reversible process is always in thermodynamic equilibrium within...
5.8K