Advances in biomaterial-based cardiac organoids.

Cardiovascular disease (CVD) is one of the important causes of death worldwide. The incidence and mortality rates are increasing annually with the intensification of social aging. The efficacy of drug therapy is limited in individuals suffering from severe heart failure due to the inability of myocardial cells to undergo regeneration and the challenging nature of cardiac tissue repair following injury. Consequently, surgical transplantation stands as the most efficient approach for treatment. Nevertheless, the shortage of donors and the considerable number of heart failure patients worldwide, estimated at 26 million, results in an alarming treatment deficit, with only around 5000 heart transplants feasible annually. The existing major alternatives, such as mechanical or xenogeneic hearts, have significant flaws, such as high cost and rejection, and are challenging to implement for large-scale, long-term use. An organoid is a three-dimensional (3D) cell tissue that mimics the characteristics of an organ. The critical application has been rated in annual biotechnology by authoritative journals, such as Science and Cell. Related industries have achieved rapid growth in recent years. Based on this technology, cardiac organoids are expected to pave the way for viable heart repair and treatment and play an essential role in pathological research, drug screening, and other areas. This review centers on the examination of biomaterials employed in cardiac repair, strategies employed for the reconstruction of cardiac structure and function, clinical investigations pertaining to cardiac repair, and the prospective applications of cardiac organoids. From basic research to clinical practice, the current status, latest progress, challenges, and prospects of biomaterial-based cardiac repair are summarized and discussed, providing a reference for future exploration and development of cardiac regeneration strategies.

Biodegradable nanotheranostics with hyperthermia-induced bubble ability for ultrasound imaging-guided chemo-photothermal therapy.

BACKGROUND: Theranostics, elaborately integrating both therapeutic and diagnostic functions into a nanoplatform holds great potential for precision cancer medicine. METHODS: Herein, a biodegradable theranostic nanoplatform with hyperthermia-induced bubble ability for highly efficient ultrasound (US) imaging-guided chemo-photothermal therapy of breast tumors was developed. The prepared nanoparticles consisted of polydopamine (PDA)-modified hollow mesoporous organosilica nanoparticles (HMONs) with approximately 75 nm in diameter for doxorubicin (DOX) loading and perfluoropentane (PFP) filling. In addition, the pH-sensitive PDA coating served as both gatekeeper controlling DOX release and photothermal agent for inducing hyperthermia. RESULTS: Such nanoplatform (PDA@HMONs-DOX/PFP, PHDP) provides efficient loading (328 mg/g) and controllable stimuli-responsive release of DOX for chemotherapy. The incorporated disulfide bonds in the framework of HMONs endowed nanoparticles with intrinsic glutathione-responsive biodegradability and improved biocompatibility. Benefiting from the hyperthermia upon an 808-nm laser irradiation of PDA, the liquid-gas phase transition of the loaded PFP was induced, resulting in the generation of the nanobubbles, followed by the coalescence into microbubbles. This conversation could enhance the tumor cell uptake of nanoparticles, as well as intensify the US imaging signals. In addition, a synergistic therapeutic effect of our fabricated nanoplatform on cells/tumor growth effect has been systematically evaluated both in vitro and in vivo. CONCLUSION: Therefore, such "all-in-one" PHDP nanoparticles with satisfactory biocompatibility and biodegradability, hyperthermia-induced bubble ability and simultaneous US imaging performance hold great potential for cancer nanotheranostics.

Targeted delivery of biodegradable nanoparticles with ultrasound-targeted microbubble destruction-mediated hVEGF-siRNA transfection in human PC-3 cells in vitro.

A potentially viable approach for treating late-stage prostate cancer is gene therapy. Successful gene therapy requires safe and efficient delivery systems. In this study, we report the efficient delivery of small interfering RNA (siRNA) via the use of biodegradable nanoparticles (NPs) made from monomethoxypoly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly-l-lysine (mPEG-PLGA-PLL) triblock copolymers. On the basis of previous findings, cyclic Arg-Gly-Asp (cRGD) peptides were conjugated to NPs to recognize the target site, integrin αvß3, expressed in high levels in PC-3 prostate cancer cells. The suppression of angiogenesis by the downregulation of vascular endothelial growth factor (VEGF) expression has been widely used to inhibit the growth of malignant tumors. In our study, human VEGF (hVEGF)-siRNA was encapsulated in NPs to inhibit VEGF expression in PC-3 cells. Concurrently, sonoporation induced by ultrasound-targeted microbubble destruction (UTMD) was utilized for the delivery of siRNA-loaded NPs. Our results showed low cytotoxicity and high gene transfection efficiency, demonstrating that the targeted delivery of biodegradable NPs with UTMD may be potentially applied as new vector system for gene delivery.