Selectively Sensitizing Malignant Cells to Photothermal Therapy Using a CD44-Targeting Heat Shock Protein 72
Shouju Wang1,2, Ying Tian1,2, Wei Tian1
1Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, P.R. China.
Abstract:
Selectively enhance the therapeutic efficacy to malignancy is one of the most important issues for photothermal therapy (PTT). However, most solid tumors, such as triple negative breast cancer (TNBC), do not have identifiable surface markers to distinguish themselves from normal cells, thus it is challenging to selectively identify and eliminate those malignances by PTT. In this report, we hypothesized that, by targeting CD44 (one TNBC-overexpressed surface molecule) and depleting heat shock protein 72 (HSP72, one malignancy-specific-overexpressed thermotolerance-related chaperone) subsequently, the TNBC could be selectively sensitized to PTT and improve the accuracy of treatment. To this end, a rationally designed nanosystem gold nanostar (GNS)/siRNA against HSP72 (siHSP72)/hyaluronic acid (HA) was successfully constructed using a layer-by-layer method. Hydrodynamic diameter and zeta potential analysis demonstrated the formation of GNS/siHSP72/HA having a particle size of 73.2 ± 3.8 nm and a negative surface charge of -18.3 ± 1.6 mV. The CD44-targeting ability of GNS/siHSP72/HA was confirmed by the flow cytometer, confocal microscopic imaging, and competitive binding analysis. The HSP72 silencing efficacy of GNS/siHSP72/HA was ∼95% in complete culture medium. By targeting CD44 and depleting HSP72 sequentially, GNS/siHSP72/HA could selectively sensitize TNBC cells to hyperthermia and enhance the therapeutic efficacy to TNBC with minimal side effect both in vitro and in vivo. Other advantages of GNS/siHSP72/HA included easy synthesis, robust siRNA loading capacity, endosome/lysosome escaping ability, high photothermal conversion efficacy and superior hemo- and biocompatibility.
Insights
This study developed a novel nanosystem to target triple-negative breast cancer (TNBC) cells. The system enhances photothermal therapy (PTT) efficacy by targeting CD44 and depleting heat shock protein 72 (HSP72), improving treatment accuracy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Photothermal therapy (PTT) faces challenges in selectively targeting solid tumors like triple-negative breast cancer (TNBC) due to a lack of distinct surface markers.
- Overexpressed surface molecules (CD44) and malignancy-specific chaperones (heat shock protein 72, HSP72) present potential targets for selective cancer treatment.
Purpose of the Study:
- To develop a targeted nanosystem for selective sensitization of TNBC to PTT.
- To investigate the combined targeting of CD44 and depletion of HSP72 for enhanced PTT efficacy and accuracy.
Main Methods:
- A layer-by-layer method was used to construct a gold nanostar (GNS)/siRNA against HSP72 (siHSP72)/hyaluronic acid (HA) nanosystem.
- Characterization included hydrodynamic diameter, zeta potential, CD44-targeting confirmation (flow cytometry, confocal microscopy), and HSP72 silencing efficacy assessment.
- In vitro and in vivo studies evaluated the therapeutic efficacy and side effects of the nanosystem in TNBC models.
Main Results:
- The GNS/siHSP72/HA nanosystem exhibited a particle size of 73.2 ± 3.8 nm and a negative surface charge.
- Confirmed CD44-targeting ability and achieved approximately 95% HSP72 silencing efficacy.
- Demonstrated selective sensitization of TNBC cells to hyperthermia, enhancing therapeutic efficacy with minimal side effects both in vitro and in vivo.
Conclusions:
- The rationally designed GNS/siHSP72/HA nanosystem effectively targets CD44 and depletes HSP72 in TNBC.
- This sequential targeting approach selectively sensitizes TNBC to PTT, improving treatment accuracy and minimizing side effects.
- The nanosystem offers advantages including easy synthesis, high siRNA loading, endosomal escape, efficient photothermal conversion, and good biocompatibility.
More Related Videos
07:47Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance
Published on: December 13, 2015
08:03Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
