Selectively Sensitizing Malignant Cells to Photothermal Therapy Using a CD44-Targeting Heat Shock Protein 72 Depletion Nanosystem

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.

Doxorubicin-Loaded Melanin Particles for Enhanced Chemotherapy in Drug-Resistant Anaplastic Thyroid Cancer Cells

“…One challenge of successful drug loading is to identify the appropriate mass ratio of drug to carrier, such that the nanoparticles can retain colloidal stability after drug loading, with minimal interparticle bridging [17]. To optimize the mass ratio for drug loading, the hydrodynamic diameter and zeta potential of Dox-MNPs obtained at different mass ratios were measured.…”

Non-Platinum Metal Complexes as Potential Anti-Triple Negative Breast Cancer Agents

“…In this way, NPMBC seem to have good in vivo pharmacokinetic properties. They are absorbed quickly into plasma [16,39,44,52], the circulation time in the bloodstream is long [42], their uptake in the tumor tissue is significant [16,28,32,37,39,41,42,44,46,51,52,60,70], their accumulation in organs (brain, liver, kidney, spleen, heart, lung, and intestine) is low [16,28,39,41,42,44,51,52,55] and the clearing rate is good [51].…”

“…NPMBC possess cytotoxic activity per se [39,66,67,69]; however, their main applications are related to their ability to act as radiosensitizers in cancer cells through the induction of G2/M phase cell cycle arrest [36,47,66], as agents for PCT applications [14,28,29,37,63] or as transmembrane carriers for the controlled release and targeted delivery of anticancer drugs increasing their cellular uptake [30,39,40], among others [47,64]. Cancer cells in a tumor are very heterogeneous, that is, they differ in marker expression, morphology, proliferation capacity, growth stage, etc.…”

“…However, both cisplatin chemotherapies and its analogs have been shown to have major drawbacks (i.e., intrinsic and acquired chemoresistance, high general toxicity and limited spectrum of activity) [26] which have motivated extensive investigations into alternative metal-based cancer therapies that effectively target both cancer cell proliferation and metastasis. In this sense, we can mention chemotherapy with gold compounds [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46]-because they are nontoxic, nonimmunogenic and have good photothermal and optical properties, biocompatibility and stability [40,47,48]-and also with copper [49][50][51], ruthenium [16,[52][53][54][55][56][57][58][59], iron [56,[60][61][62][63][64][65], palladium [50], silver [66,…”

Facile synthesis of Prussian blue nanoparticles as pH-responsive drug carriers for combined photothermal-chemo treatment of cancer

“…8 Subsequently, various NIR-absorbing nanomaterials, such as gold nanostructures, [9][10][11] carbon-based nanomaterials, [12][13][14][15][16] copper sulde nanoparticles, 6,17,18 palladium nanosheets, 19 transition-metal dichalcogenides nanosheets (e.g., MoS 2 , WS 2 , etc. ), 20,21 and a number of organic polymers nanoparticles, [22][23][24][25] have been developed as drug delivery vehicles for combined photothermal-chemo treatment of cancer cells.…”