Xiaohua Zheng

Self-Assembly of Porphyrin–Paclitaxel Conjugates Into Nanomedicines: Enhanced Cytotoxicity due to Endosomal Escape

Nanomedicines assembled directly from drug molecules possess several advantages, including precise molecular structure and high content of drugs. Herein, porphyrin-paclitaxel conjugates (Py-s-s-PTX) were synthesized by using a disulfide bond as a linker. The Py-s-s-PTX could self-assemble into nanoparticles (Py-s-s-PTX NPs) with a size of about 100 nm via disulfide-induced assembly. Py-s-s-PTX NPs are highly stable under biological conditions and could be destroyed in the presence of reducing agents as revealed by dynamic light scattering. The obtained Py-s-s-PTX NPs could be internalized by cancer cells via endocytosis and disassociated in the reducing cytoplasm, thus releasing PTX in cancer cells. Endosomal escape triggered upon irradiation could enhance the cytotoxicity of paclitaxel, and Py-s-s-PTX NPs possess cytotoxicity comparable to that of free PTX. We believe that this disulfide-assembled nanomedicine represents a new and important development for chemotherapy in cancer therapy.

Nanoscale Fluorescent Metal–Organic Framework@Microporous Organic Polymer Composites for Enhanced Intracellular Uptake and Bioimaging

Polymer-modified metal-organic frameworks combine the advantages of both soft polymers and crystalline metal-organic frameworks (MOFs). It is a big challenge to develop simple methods for surface modification of MOFs. In this work, MOF@microporous organic polymer (MOP) hybrid nanoparticles (UNP) have been synthesized by epitaxial growth of luminescent boron-dipyrromethene (BODIPYs)-imine MOPs on the surface of UiO-MOF seeds, which exhibit low cytotoxicity, smaller size distribution, well-retained pore integrity, and available functional sites. After folic acid grafting, the enhanced intracellular uptake and bioimaging was validated.

Porphyrin‐Based Carbon Dots for Photodynamic Therapy of Hepatoma

Porphyrin-containing carbon dots (CDs) possess ultrasmall size, excellent water solubility, and photostability. These CDs can effectively generate cytotoxic singlet oxygen upon irradiation, and induce the cell apoptosis. Photodynamic ability of CDs inhibits the growth of hepatoma. This work not only sheds light on developing functional carbon dots, but also highlights the importance of special-structure precursor molecules in synthesizing functional CDs.

PEG‐Induced Synthesis of Coordination‐Polymer Isomers with Tunable Architectures and Iodine Capture

Controllable synthesis of coordination polymer (CP) isomers and revealing their structure-property relationships remain enormous challenges. Three new supramolecular isomers have been synthesized by tuning the poly(ethylene glycol) (PEG) content in the feed. These supramolecular isomers have the same framework formula of [Cu2 I2 (tppe)] and different architectures from the classical 2D stacking framework to a 3D entangled system with the coexistence of interpenetration and polycatenation, and a 3D topological framework. Interestingly, these CPs could be utilized for capturing iodine molecules. According to multiple complementary experiments and crystallographic analyses, iodine capture is mainly based on halogen-bond interactions in the inorganic {Cu2 I2 } building blocks of the framework. The present study describes a structure-property relationship in supramolecular isomerism with distinct topological structures.

Light-Activatable Red Blood Cell Membrane-Camouflaged Dimeric Prodrug Nanoparticles for Synergistic Photodynamic/Chemotherapy

Biomimetic approach offers numerous opportunities to design therapeutic platforms with enhanced antitumor performance and biocompatibility. Herein we report red blood cell membrane-camouflaged nanoparticles (RBC(M(TPC-PTX))) for synergistic chemo- and photodynamic therapy (PDT). Specifically, the inner core is mainly constructed by reactive oxygen species (ROS)-responsive PTX dimer (PTX2-TK) and photosensitizer 5,10,15,20-tetraphenylchlorin (TPC). In vitro experiments show that the prepared RBC(M(TPC-PTX)) is readily taken up into endosomes. Under appropriate light irradiation, the TPC can generate ROS, not only for PDT but also for triggering PTX2-TK cleavage and on-demand PTX release for chemotherapy. In vivo results show that the coating of RBC membrane prolongs blood circulation and improves tumor accumulation. The combination of chemo- and photodynamic therapy enhances anticancer therapeutic activity, and light-triggered drug release reduces systematic toxicity. All these characteristics render the described technology extremely promising for cancer treatment.

Second Near-Infrared Conjugated Polymer Nanoparticles for Photoacoustic Imaging and Photothermal Therapy

Photothermal conversion in the second near-infrared (NIR-II) window allows deeper penetration and higher exposure to lasers, but examples of NIR-II photothermal agents are mainly formulated by inorganic compounds. In view of the underlying influence of inorganic materials, a novel NIR-II photothermal nanoagent based on a narrow band gap D-A conjugated polymer (TBDOPV-DT) with 2,2-bithiophene as the donor and thiophene-fused benzodifurandione-based oligo( p-phenylenevinylene) as the acceptor has been developed. More importantly, TBDOPV-DT nanoparticles (TBDOPV-DT NPs) are demonstrated to combine excellent photoacoustic imaging (PAI) and photothermal therapy (PTT) ability. TBDOPV-DT NPs exhibit dramatic photostability and heating reproducibility with a photothermal conversion efficiency of 50%. Especially, the NPs possess a remarkable PTT effect toward cancer cells in vitro and can eliminate tumor cells completely in vivo under 1064 nm laser irradiation, while no appreciable side effects have been observed. This study achieves PAI-guided cancer therapy and sheds light on the future of using organic polymer NPs for the NIR-II PTT of cancer.

Photothermally induced accumulation and retention of polymeric nanoparticles in tumors for long-term fluorescence imaging

The development of long-term tumor imaging is of great importance for effective theranostic systems. In this study, a temperature-responsive poly(ether amine) with a phase transition temperature around 43 °C was used to encapsulate indocyanine green (ICG), which is a near infrared fluorescent and photothermal agent. Upon photothermal treatment, the polymeric nanoparticles underwent an increase in size from the nano- to the microscale. The prepared ICG-loaded PEAs exhibited significant stability against photobleaching and excellent NIR imaging ability. The increase in particle size resulted in the accumulation and retention of nanoparticles at the tumor site upon photothermal treatment. The accumulation of nanoparticles facilitated long-term imaging of the tumor for up to 30 days after one injection. This study highlights the potential of the rational design of polymer nanoparticles for bioimaging and diagnostics.

GSH-triggered size increase of porphyrin-containing nanosystems for enhanced retention and photodynamic activity

Long retention of therapeutic agents in tumors is imperative for improving the therapeutic index. In this work, the GSH responsive porphyrin molecule (TPP 1) was synthesized, which is amphiphilic and linked by a disulfide bond. TPP 1 molecules could self-assemble into nanoparticles (TPP 1 NPs) with a size of about 100 nm in aqueous solution. The TPP 1 NPs exhibited high stability under different conditions and could form into large microparticles in the presence of glutathione (GSH). The TPP 1 NPs could be internalized by cancer cells, and they emitted enhanced red fluorescence compared to that of TPP 2 NPs (non-sensitive NPs) when cells were pretreated with GSH. In addition, in vitro MTT assays showed that TPP 1 NPs were biocompatible and could further be used as photosensitizers in nanoparticle formation. The cellular photodynamic activity of TPP 1 NPs was obviously higher than that of TPP 2 NPs, due to the increasing retention of TPP in cancer cells, which will generate more reactive oxygen species in cancer cells under light irradiation. These results highlight the potential of developing stimulus responsive nanoparticles for enhanced retention and improved therapeutic outcome.

Hypoxia-Triggered Nanoscale Metal–Organic Frameworks for Enhanced Anticancer Activity

The oxygen-dependent feature of most photosensitizers (PSs) and the aggravated hypoxia tumor microenvironment seriously impede the photodynamic therapy (PDT) effectiveness. However, this undesirable impediment can be utilized to further trigger the activation of hypoxia-sensitive prodrugs. Moreover, a combined therapy can be used by associating PDT with hypoxia-activated chemotherapy. Herein, a multifunctional Hf-porphyrin nanoscale metal-organic framework (NMOF) platform [Hf/tetra(4-carboxyphenyl)porphine (TCPP)] has been synthesized, with a high porphyrin loading capacity and a well-ordered coordination array preventing porphyrin self-quenching, thus greatly improving the generation efficiency of reactive oxygen species (ROS), which is helpful for PDT. As-synthesized Hf-TCPP nanoparticles possess more than 50 wt % of TCPP PS content, good crystallization, and a large Brunauer-Emmett-Teller surface for further loading the hypoxia-activated prodrug [tirapazamine (TPZ)] in a high-loading content. Additionally, subsequent surface modification with a dopamine-derived polymer (DOPA-PIMA-mPEG) significantly improves their dispersibility and structural stability, and the controlled release kinetics of TPZ. Such a nanoplatform can efficiently produce ROS for PDT upon irradiation, and also the depletion of the oxygen could further aggravate the hypoxic environment of tumors to induce the activation of TPZ for achieving an enhanced treatment efficacy. This work demonstrates the great advantages of an NMOF-based platform in antitumor therapies for combined PDT and hypoxia-activated chemotherapy.

Self-assembled organic nanorods for dual chemo-photodynamic therapies

Photodynamic therapy (PDT) and chemotherapy have been extensively developed as effective approaches against cancer. Herein, we constructed organic nanorods by rational co-assembly of photosensitizer, di-iodinated borondipyrromethene (BDP-I2), and chemical anticancer drug, paclitaxel (PTX). The physico- and photochemical properties of the obtained nanorods were carefully investigated. BDP-I2 was selected for its high singlet oxygen (1O2) quantum yields. And the corresponding 1O2 generation ability and photodynamic effect were evaluated both in vitro and in vivo. The accelerated endosomal escape of the nanorods induced by the photodynamic effect enhanced the chemotherapeutic efficacy of PTX. We believe that this synergetic nanomedicine represents a new development for antitumor chemophotodynamic therapy.