Host–Guest Polypyrrole Nanocomplex for Three‐Stimuli‐Responsive Drug Delivery and Imaging‐Guided Chemo‐Photothermal Synergetic Therapy of Refractory Thyroid Cancer

Abstract

Despite the good prognosis of the low‐risk thyroid cancer, there are no truly effective treatments for radioactive iodine‐refractory thyroid cancer. Herein, a novel theranostic nanoplatform, as well as a smart doxorubucin (DOX) delivery system is fabricated. Gelatin‐stabilized polypyrrole nanoparticles are reported for the first time. The combination of gelatin‐stabilized polypyrrole and cyclodextrin‐DOX complexes enabling three‐stimuli‐controlled drug delivery, including the enzyme‐sensitive, pH‐sensitive and photothermal‐sensitive drug release, exhibiting a new way to equip photothermal agents with precisely controlled drug delivery. Anti‐galectin‐3 antibodies are utilized as the targeting molecules of nanoparticles in the first time, which surprisingly increase intracellular DOX uptake by enhanced clathrin‐mediated endocytosis, showing galectin‐3 can be employed as a highly efficient target of drug delivery systems. The nanoparticles achieve excellent photoacoustic imaging effect, enabled chemo‐photothermal combined therapy with pinpointed drug delivery. Compared to free DOX, these multifunctional nanoparticles decrease the heart damage, but greatly increase the tumor/heart ratio of DOX concentration by 12.9‐fold. The tumors are completely eradicated without any recurrence after the in vivo combined therapy. To the best of the authors' knowledge, this is also the first report to apply photoacoustic imaging‐guided chemo‐photothermal therapy for thyroid cancer, showing great potential to solve the dilemma in thyroid cancer therapy.

Cyclodextrin Based Nanoparticles for Drug Delivery and Theranostics

“…[143][144][145] Table 4. [149][150][151][152][153][154][155][156][157][158][159][160][161][162][163]…”

A Dual pH-Responsive DOX-Encapsulated Liposome Combined with Glucose Administration Enhanced Therapeutic Efficacy of Chemotherapy for Cancer

“…The in vitro cellular uptake of Cy5.5 fluorescent liposomes was evaluated in MDA-MB-435S cancer cells and HeLa cancer cells. Briefly, the cells were seeded at a density of 2×10 4 per well in glass bottom cell culture dishes and incubated for 24 h at 37 °C. Then, 100 μL fluorescent liposomes (at a final Cy5.5 concentration of 20 μM) with different pH values (6.0 and 7.4) was added and incubated for 1 h. The cells were washed twice with ice-cold PBS and further analyzed by a FACSCalibur system.…”

“…CLSM was used to study the cellular uptake and intracellular release behaviors of DOX-loaded liposomes in MDA-MB-435S. Briefly, the cells were seeded at a density of 2×10 4 per well in glass bottom cell culture dishes and incubated for 24 h at 37 °C. Then, 100 μL of free DOX or DOX-loaded liposomes with different pH values was added and incubated for 1 h. The cells were washed twice with ice-cold PBS.…”

“…Tumor microenvironment (TME), supporting the survival and development of cancer cells, has the special physical and chemical characteristic, such as low concentration of oxygen and low pH value, which not only play a key role in tumor progression and metastasis but also has an obvious impact on the therapeutic efficacy of tumors. [1][2][3][4] In the acidic microenvironment of tumors, weakly alkaline drug molecules are easily protonated, preventing them from entering tumor cells and thus causing drug resistance. Therefore, investigating the regulatory effect of acidic TME on chemotherapy will help improving the resistance of chemotherapeutic drugs, thereby increasing the response rate and treatment efficacy of chemotherapy.…”

A pH‐Sensitive Self‐Assembled and Carrier‐Free Nanoparticle Based on Charge Reversal for Enhanced Synergetic Chemo‐Phototherapy

“…[12][13][14] More and more researchers pay attention to multifunctional NPs, a blend of different therapeutic modal demonstrated ideal and effective therapeutic efficiency in recent years (e.g., the combination of chemotherapy and immune therapy, phototherapy in association with chemotherapy, etc.). [14][15][16][17] Photodynamic therapy (PDT), as a reliably and noninvasively clinical cancer therapy, wins the researchers' great interests. [18] Generally, photosensitizers were used to achieve photodynamic therapy, fluorescence (FL) imaging and photoacoustic (PA) imaging.…”