Supramolecular Polymer-Based Nanomedicine: High Therapeutic Performance and Negligible Long-Term Immunotoxicity.

Nanomedicines have achieved several breakthroughs in cancer treatment over the past decades; however, their potential immunotoxicities are ignored, which results in serious adverse effects and greatly reduces the potential in clinical translation. Herein, we innovatively develop a theranostic supramolecular polymer using ß-cyclodextrin as the host and camptothecin (CPT) as the guest linked by a glutathione-cleavable disulfide bond. The supramolecular polymerization remarkably increases the solubility of CPT by a factor of 232 and effectively inhibits its lactone ring opening in physiological environment, which is favorable for intravenous formulation and maintenance of the therapeutic efficacy. Supramolecular nanoparticles can be prepared through orthogonal self-assembly driven by π-π stacking interaction, host-guest complexation, and hydrogen bonds. The sophisticated nanomedicine constructed from the obtained supramolecular polymer can be specifically delivered to tumor sites and rapidly excreted from body after drug release, thus effectively avoiding systemic toxicity, especially long-term immunotoxicity. In vivo investigations demonstrate this supramolecular nanomedicine possesses superior antitumor performance and antimetastasis capability. This pioneering example integrating the advantages of the dynamic nature of supramolecular chemistry and nanotechnology provides a promising platform for cancer theranostics.

Advanced Biomaterials and Processing Methods for Liver Regeneration: State-of-the-Art and Future Trends.

Liver diseases contribute markedly to the global burden of mortality and disease. The limited organ disposal for orthotopic liver transplantation results in a continuing need for alternative strategies. Over the past years, important progress has been made in the field of tissue engineering (TE). Many of the early trials to improve the development of an engineered tissue construct are based on seeding cells onto biomaterial scaffolds. Nowadays, several TE approaches have been developed and are applied to one vital organ: the liver. Essential elements must be considered in liver TE-cells and culturing systems, bioactive agents or growth factors (GF), and biomaterials and processing methods. The potential of hepatocytes, mesenchymal stem cells, and others as cell sources is demonstrated. They need engineered biomaterial-based scaffolds with perfect biocompatibility and bioactivity to support cell proliferation and hepatic differentiation as well as allowing extracellular matrix deposition and vascularization. Moreover, they require a microenvironment provided using conventional or advanced processing technologies in order to supply oxygen, nutrients, and GF. Herein the biomaterials and the conventional and advanced processing technologies, including cell-sheets process, 3D bioprinting, and microfluidic systems, as well as the future trends in these major fields are discussed.

Stromal cell-derived factor-1α-encapsulated albumin/heparin nanoparticles for induced stem cell migration and intervertebral disc regeneration in vivo.

Intervertebral disc (IVD) degeneration may cause many diseases and pain. Stem cell migration toward the site of IVD degeneration is a key factor for IVD regeneration. In the current study, we prepared albumin/heparin nanoparticles (BHNPs) as injectable carriers of stromal cell-derived factor-1α (SDF-1α, also known as C-X-C motif chemokine 12), a powerful chemoattractant for the homing of bone marrow resident mesenchymal stem cells (MSCs), for protection of the molecule against degradation for a sustained release. The NPs have relatively uniform small size, with a diameter of about 110 nm. The NPs possess a high loading capacity of SDF-1α with a sustained release profile. The bioactivity of the obtained BHNPs/SDF was then studied in vitro and in vivo. The BHNPs/SDF can induce migration of MSCs in a dose-dependent manner in vitro. After injected into the damaged disc, BHNPs/SDF induce much better regeneration of annulus fibrosus and nucleus pulposus, compared to SDF-1α and BHNPs alone, evidenced with better histological grade scores and higher expression of SOX9, Aggrecan, and Collagen type II at the level of both mRNA and protein. This study provides a simple nanoplatform to load SDF-1α and protect it against degradation, with potential application in inductive tissue regeneration in vivo. STATEMENT OF SIGNIFICANCE: Stem cell migration toward the site of IVD degeneration is a key event to promote IVD regeneration. In the current study, we prepared albumin/heparin nanoparticles (BHNPs) as injectable carriers to protect SDF-1α against degradation and for the sustained release of the molecule. After injected into the damaged disc, BHNPs/SDF induced much better regeneration of IVD, compared to SDF-1α and BHNPs alone. This study provides a simple nanoplatform to load SDF-1α and protect it from degradation, with potential application in inductive tissue regeneration in vivo.

Doxorubicin-conjugated pH-responsive gold nanorods for combined photothermal therapy and chemotherapy of cancer.

Cancer chemotherapy can be hindered by drug resistance which leads to lower drug efficiency. Here, we have developed a drug delivery system that tethers doxorubicin to the surface of gold nanorods via a pH-sensitive linkage (AuNRs@DOX), for a combined photothermal and chemical therapy for cancer. First, AuNRs@DOX is ingested by HepG2 liver cancer cells. After endocytosis, the acidic pH triggers the release of doxorubicin, which leads to chemotherapeutic effects. The gold nanorods are not only carriers of DOX, but also photothermal conversion agents. In the presence of an 808 nm near-infrared laser, AuNRs@DOX significantly enhance the cytotoxicity of doxorubicin via the photothermal effect, which induces elevated apoptosis of hepG2 cancer cells, leading to better therapeutic effects in vitro and in vivo.

Folic acid modified cell membrane capsules encapsulating doxorubicin and indocyanine green for highly effective combinational therapy in vivo.

A combination of chemotherapy and phototherapy has emerged as a promising strategy for cancer treatment. To achieve effective combinational therapy of cancer with reduced toxicity, it is highly desirable to improve the targeting of chemotherapeutic and near-infrared photosensitizers to enhance their accumulation in tumor. Here we report a novel tumor targeting cell membrane capsule (CMC), originate from living cells, to load doxorubicin hydrochloride (DOX) and indocyanine green (ICG), for combinational photo-chemotherapy against cancer. As a result, folic acid modified CMC (CMC-FA, with a diameter about 200 nm and a FA density of 0.4 molecule/nm2) showed 3-4 fold higher cell uptake by cancer cells in vitro and 2.3 times higher accumulation in mouse cancer xenografts in vivo than pristine CMC. DOX and ICG with therapeutically significant concentrations can be sequentially encapsulated into CMC-FA by temporary permeating the plasma membranes with high efficiency. The systematic administration of cancer targeting CMC-FA loaded with DOX and ICG could significantly inhibit tumor growth in mouse xenografts in the presence of a near-infrared light at 808 nm, without noticeable toxicity. These findings suggest that cancer targeting CMC may have considerable benefits in drug delivery and combinational cancer therapy. STATEMENT OF SIGNIFICANCE: A combination of chemotherapy and photothermal/photodynamic therapy has emerged as a promising strategy for cancer therapy. In current study, a novel cancer targeting cell membrane capsule (CMC-FA), originate from living cells and surface modified with folic acid, was developed to load doxorubicin hydrochloride (DOX) and indocyanine green (ICG), for combinational photo-chemotherapy against cancer. The systematic administration of drug loaded CMC-FA can significantly inhibit tumor growth in mouse xenografts in the presence of a near-infrared light at 808 nm, without noticeable toxicity. This study provides a simple and robust strategy to develop biocompatible therapeutic cell membrane capsules, holds strong translational potential in precise cancer treatment.