Finely Tuned Thermo‐Responsive Block Copolymer Micelles for Photothermal Effect‐Triggered Efficient Cellular Internalization

Abstract

Although biodegradable amphiphilic block copolymer micelles have been widely applied in the clinical applications as drug delivery nanocarriers, low-efficiency cellular internalization frequently reduces therapeutic efficacy of the loaded drugs. Here, photothermal effect-promoted cellular internalization of finely tuned thermo-responsive amphiphilic biodegradable block copolymer nanocarriers via noninvasive stimuli of near-infrared (NIR) light irradiation is demonstrated. Amphiphilic block copolymers, poly(ε-caprolactone)-block-poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (PCL-b-P(NIPAM-co-DMA)), are prepared with finely tuned compositions of P(NIPAM-co-DMA) for desirable lower critical solution temperature of the block copolymer micelles in aqueous solution. The block copolymers are then used to co-encapsulate doxorubicin and indocyanine green, which show high encapsulation efficiency and significant photothermal effect upon exposure to NIR light irradiation. The photothermal effect-induced collapse and hydrophilic-to-hydrophobic transition of P(NIPAM-co-DMA) shells significantly enhance the interactions between drug-loaded micelles and cell membranes, which dramatically promote the cellular internalization of the micelles and therapeutic efficacy of loaded anticancer drugs.

An NIR-Guided Aggregative and Self-Immolative Nanosystem for Efficient Cancer Targeting and Combination Anticancer Therapy

“…The water sample demonstrated a slight temperature increase to about 24 °C after 5 min of NIR irradiation, whereas the temperature of the DIMs sample increased significantly, especially in the case of the more concentrated DIMs sample, which reached 43 °C. It was worth noting that the eventual temperature of the DIMs solution was higher than that of the free ICG solutions at the same concentrations, attributing to the increase of absorbance intensity for encapsulated ICG molecules at 808 nm. − …”

Thermoresponsive and Biodegradable Amphiphilic Block Copolymers with Pendant Functional Groups

“…If amphiphilic block copolymer solutions (as thermoresponsive hydrogel) can be prepared at room temperature, biologics, such as drugs and cells, can easily be mixed into the copolymer [3]. Therefore, various amphiphilic block copolymers have been employed as candidates for use as thermoresponsive polymers [4][5][6][7][8][9][10]. The thermal response is thought to occur via the formation of individual micelles, which then coaggregate and form hydrophobic domains; this causes the solution-to-hydrogel phase transition [3].…”

“…The precipitated mixture was solubilized in DCM and washed three times with distilled water (DW). The organic phase was extracted, dried over anhydrous MgSO4 and the solvent was removed by evaporation to obtain MCL-(NH 2 ) 10 . MCL-(NH 2 ) 3 , MCL-(NH 2 ) 5 , and MCL-(NH 2 ) 15 were prepared according to the same procedure.…”

Conjugated Polymer/Graphene Oxide Complexes for Photothermal Activation of DNA Unzipping and Binding to Protein

“…The interactions and structural changes of biomolecules are an important part of the life process, and the intracellular processes are closely related to the DNA–protein interactions. − As a protein that specifically binds to DNA, single-stranded binding protein (SSBP) extracted from sulfolobus solfataricus binds 20 bases in the form of homologous through hydrophobic and π–π interaction and protects ssDNA from damage. − As an essential basic protein in life process, SSBP plays an important role in DNA replication, repair, and recombination. − Therefore, detection of SSBP is of great importance in studying the function of protein, , treatment of related diseases, and biological detection. , Recent studies revealed mitochondrial diseases, liver cancer, and some neurological diseases are also associated with the interactions between SSBP and DNA , as well as the structural change in DNA. , Therefore, the regulation of the interactions between SSBP and DNA has always been the focus of attention for researchers . However, most of current techniques are limited to detect the presence of SSBP and cannot achieve the regulation of interaction between SSBP and DNA. ,,, Therefore, developing a new therapy strategy to regulate DNA and proteins interaction is becoming an important issue. , Photothermal effect is an emerging alternative to thermally stimulate cellular processes by applying near-infrared (NIR) light-adsorbing agents to convert energy to heat, − leading to the deep penetration and increased local temperature, which is promising for control the thermosensitive processes. Because of the high penetration depth, noninvasiveness, and minimized adverse side effects, photothermal effect is emerging as a promising method for cancer therapy and bimolecular regulation. − …”