Theoretical perspective on synthetic man-made life:Learning from the origin of life

Creating a man-made life in the laboratory is one of life science's most intriguing yet challenging problems.Advances in synthetic biology and related theories,particularly those related to the origin of life,have laid the groundwork for further exploration and understanding in this field of artificial life or man-made life.But there remains a wealth of quantitative mathematical models and tools that have yet to be applied to this area.In this paper,we review the two main approaches often employed in the field of man-made life:the top-down approach that reduces the complexity of extant and existing living systems and the bottom-up approach that integrates welldefined components,by introducing the theoretical basis,recent advances,and their limitations.We then argue for another possible approach,namely"bottom-up from the origin of life":Starting with the establishment of autocatalytic chemical reaction networks that employ physical boundaries as the initial compartments,then designing directed evolutionary systems,with the expectation that independent compartments will eventually emerge so that the system becomes free-living.This approach is actually analogous to the process of how life originated.With this paper,we aim to stimulate the interest of synthetic biologists and experimentalists to consider a more theoretical perspective,and to promote the communication between the origin of life community and the synthetic man-made life community.

A nanomedicine approach enables co-delivery of cyclosporin A and gefitinib to potentiate the therapeutic efficacy in drug-resistant lung cancer

Drug resistance,accounting for therapeutic failure in the clinic,remains a major challenge to effectively manage cancer.Cyclosporin A(CsA)can reverse multidrug resistance(MDR),especially resistance to epidermal growth factor receptor tyrosine kinase inhibitors.However,the application of both drugs in cancer therapies is hampered by their poor aqueous solubility and low bioavailability due to oral administration.CsA augments the potency of gefitinib(Gef)in both Gef-sensitive and Gef-resistant cell lines.Here,we show that the simultaneous encapsulation of CsA and Gef within polyethylene glycol-block-poly(D,L-lactic acid)(PEG-PLA)produced a stable and systemically injectable nanomedicine,which exhibited a sub-50-nm diameter and spherical structures.Impressively,the co-delivery of therapeutics via single nanoparticles(NPs)outperformed the oral administration of the free drug combination at suppressing tumor growth.Furthermore,in vivo results indicated that CsA formulated in NPs sensitized Gef-resistant cells and Gefresistant tumors to Gef treatment by inactivating the STAT3/Bcl-2 signaling pathway.Collectively,our nanomedicine approach not only provides an alternative administration route for the drugs of choice but also effectively reverses MDR,facilitating the development of effective therapeutic modalities for cancer.