Tingting Chen

pH- and NIR Light-Responsive Polymeric Prodrug Micelles for Hyperthermia-Assisted Site-Specific Chemotherapy to Reverse Drug Resistance in Cancer Treatment.

Despite the exciting advances in cancer chemotherapy over past decades, drug resistance in cancer treatment remains one of the primary reasons for therapeutic failure. IR-780 loaded pH-responsive polymeric prodrug micelles with near infrared (NIR) photothermal effect are developed to circumvent the drug resistance in cancer treatment. The polymeric prodrug micelles are stable in physiological environment, while exhibit fast doxorubicin (DOX) release in acidic condition and significant temperature elevation under NIR laser irradiation. Phosphorylcholine-based biomimetic micellar shell and acid-sensitive drug conjugation endow them with prolonged circulation time and reduced premature drug release during circulation to conduct tumor site-specific chemotherapy. The polymeric prodrug micelles combined with NIR laser irradiation could significantly enhance intracellular DOX accumulation and synergistically induce the cell apoptosis in DOX-resistant MCF-7/ADR cells. Meanwhile, the tumor site-specific chemotherapy combined with hyperthermia effect induces significant inhibition of MCF-7/ADR tumor growth in tumor-bearing mice. These results demonstrate that the well-designed IR-780 loaded polymeric prodrug micelles for hyperthermia-assisted site-specific chemotherapy present an effective approach to reverse drug resistance.

Zwitterionic Phosphorylcholine–TPE Conjugate for pH-Responsive Drug Delivery and AIE Active Imaging

Polymeric micelles have emerged as a promising nanoplatform for cancer theranostics. Herein, we developed doxorubicin (DOX) encapsulated pH-responsive polymeric micelles for combined aggregation induced emission (AIE) imaging and chemotherapy. The novel zwitterionic copolymer poly(2-methacryloyloxyethylphosphorylcholine-co-2-(4-formylphenoxy)ethyl methacrylate) (poly(MPC-co-FPEMA)) was synthesized via RAFT polymerization and further converted to PMPC-hyd-TPE after conjugation of tetraphenylethene (TPE, a typical AIE chromophore) via acid-cleavable hydrazone bonds. The AIE activatable copolymer PMPC-hyd-TPE could self-assemble into spherical PC-hyd-TPE micelles, and DOX could be loaded through hydrophobic interactions. The zwitterionic micelles exhibited excellent physiological stability and low protein adsorption due to the stealthy phosphorylcholine (PC) shell. In addition, the cleavage of hydrophobic TPE molecules under acidic conditions could induce swelling of micelles, which was verified by size changes with time at pH 5.0. The in vitro DOX release profile also exhibited accelerated release rate with pH value decreasing from 7.4 to 5.0. Fluorescent microscopy and flow cytometry studies further demonstrated fast internalization and accumulation of drug loaded PC-hyd-TPE-DOX micelles in HepG2 cells, resulting in considerable time/dose-dependent cytotoxicity. Meanwhile, high-quality AIE imaging of PC-hyd-TPE micelles was confirmed in HepG2 cells. Notably, ex vivo imaging study exhibited efficient accumulation and drug release of PC-hyd-TPE-DOX micelles in the tumor tissue. Consequently, the multifunctional micelles with combined nonfouling surface, AIE active imaging, and pH-responsive drug delivery showed great potential as novel nanoplatforms for a new generation of cancer theranostics.

Glutathione Activatable Photosensitizer-Conjugated Pseudopolyrotaxane Nanocarriers for Photodynamic Theranostics.

Photodynamic theranostics has recently been extensively explored as a promising approach for precise localization and therapy. Herein, glutathione (GSH) activatable photosensitizer (PS)-conjugated pseudopolyrotaxane nanocarriers (α-CD-ss-Ce6 NPs) are reported for enhanced photodynamic theranostics by taking advantage of the noncovalent interactions between α-cyclodextrin (α-CD) and poly(ethylene glycol). The designed α-CD-ss-Ce6 NPs are nonactivated and stable during circulation but exhibited strong photodynamic theranostics through GSH activating after arriving at tumor site. More importantly, compared to free chlorin e6 (Ce6), such kind of pseudopolyrotaxane nanocarrier can dramatically enhance Ce6 accumulation in tumor and prolong its tumor retention time, demonstrating excellent therapeutic effects after light irradiation. Overall, the designed GSH activatable PS-conjugated pseudopolyrotaxane nanocarrier possessing high-performance photodynamic therapeutic efficacy together with reduced side effects offers a promising alternative for photodynamic theranostics.

A “writing” strategy for shape transition with infinitely adjustable shaping sequences and in situ tunable 3D structures

A light “writing” strategy is developed to generate easy-to-implement, sequential and “personalized tailoring” three-dimensional (3D) shape transition by exploiting the photothermal conversion capability of polydopamine (PDA) and the shape memory effect of Nafion films. A homogeneous Nafion/PDA composite film in a stretched temporary shape and a near infrared (NIR) laser are employed as paper and pen, respectively. With localized heat generated from tunable NIR light irradiation, well controlled internal stress can be “written” into the film precisely and thus trigger complex 2D–3D shape transition instantly. The tunability and predictability of the obtained 3D shapes are verified. Compared with previous methods, such a light “writing” strategy can be used to modulate both the target shape and the shape transition process in situ at the same time with no need to tune the material compositions or structures. Stepwise shape transitions with infinitely adjustable shaping sequences are realized in this work, which is of crucial importance in constructing overlapped structures. Furthermore, the 3D shapes can be adjusted flexibly to meet on site individual requirements. This adaptability makes it a new way to tackle the contradiction between individual variation and standardized manufacturing techniques in fields like personalized healthcare.

Intracellular Dual Fluorescent Lightup Bioprobes for Image-Guided Photodynamic Cancer Therapy.

An intracellular dual fluorescent light-up bioprobe with aggregation-induced emission features and endogenously producing photosensitizer protoporphyrin IX (PpIX) abilities is designed and synthesized. The bioprobe is nonemissive in physiological environment. However, the bioprobe can selectively light up cancer cells with blue fluorescence of tetraphenylene (TPE) and red fluorescence of PpIX, owing to the release of TPE and methyl aminolevulinate after targeted internalization by cancer cells. Moreover, upon endogenous generation and accumulation of PpIX in cancer cells, efficient photodynamic ablation of cancer cells after light irradiation is demonstrated with easy regulation for optimal therapeutic efficacy. The design of such dual fluorescent light-up bioprobes might provide a new opportunity for targeted and image-guided photodynamic cancer therapy.