Traditional biopharmaceutics deals with the in vivo fate of drug dosage forms, consisting of absorption, distribution, metabolism, elimination aspects. To open new avenue on biopharmaceutics, and to address critical scientific and clinical issues, new research progresses in biopharmaceutics have been achieved in revealing the action mechanism of drug delivery systems for multidrug resistance, mitochondria, vascular mimicry(VM) channels, gene editing of cancer and cancer stem cells, and transport across the brainblood barrier(BBB), as described in the following. Circumvention of multidrug resistance in cancer by inhibiting drug efflux Cancer drug resistance is referring to the tolerance of cancer cells when treated with chemotherapy. Once the drug resistance occurs, therapeutic effect of anticancer drug would decrease significantly. Multi-drug resistance(MDR) has been evidenced in a variety of cancers, including leukemia, breast cancer, and lung cancer. Overexpressions of the ATP-binding cassette(ABC) family of proteins on the membrane of cancer cell are responsible for this type of drug resistance. Novel anti-resistant drug liposomes and nanomicelles were fabricated for blocking the drug efflux(Biomaterials. 2012, 33, 1808; Biomaterials. 2013, 34, 3366; Adv Drug Deliv Rev 2017,115, 46). Induction of apoptosis for the refractory cancer by targeting mitochondria Apoptosis is a process of programmed cell death involved in cellular stress response, and most chemotherapies kill cancer cells by apoptosis. Defects in apoptosis could confer drug resistance to chemotherapeutic agents as well, and such defects may arise from inactivation of pro-apoptotic gene expressed proteins(Bax, Bak, Bok, Bad, Bid, Bim, and p53, etc.), and from activation of anti-apoptotic gene expressed proteins(Bcl-2, Bcl-xl, Bcl-w, Bcl-1, and Bfl1/A1, etc.). There are two major drug-induced apoptosis: one involves the cell surface receptors, the other directly targets mitochondria. The structural features of mitochondria are the double membranes which lead to be negative membrane potential. Therefore, liposomes modified with cationic compounds can accumulate in mitochondria by potential force, leading to initiating a cascade of apoptotic reactions in cancer cells(Biomaterials 2013, 34, 4452; Biomaterials 2013, 34, 3626; Adv Drug Deliv Rev 2017, 115, 46).Blockage of cancer recurrence by destructing VM channels As the supply channels, vasculogenic mimicry(VM) channels provide the nutrients at the initial stage during development of cancer tissues, while angiogenic blood vessels supply the nutrients at the subsequent stages when cancer volume increases. Vasculogenic mimicry channels are the microvascular-like channels that areformed by epigenetically altered cancer cells under the condition of hypoxia when cancer volume is small(e.g., <150 mm3). The existence of supply channels facilitates the growth and the re-generation of cancer tissue after regular chemotherapy, thereby conferring drug resistance to cancer cells. Therefore, Lu and his colleagues proposed a four-stage hypothesis that the supply channels could exist in the vasculogenic mimicry channels(formed by mutated cancer cells), the mosaic channels(intermittent channels formed by mutated cancer and endothelial cells), angiogenic blood channels(fully formed by endothelial cells), and vasculaogenic mimicry channels(relapsed channels formed by re-generated cancer cells). To destroy vasculogenic mimicry channels in invasive breast cancer, several kinds of dual-functional drug liposomes have been fabricated(Biomaterials 2014, 35, 5591; J Biomed Nanotechnol 2015, 11, 1339; Adv Drug Deliv Rev 2017,115, 46).Elimination of cancer stem cells by direct killing and gene-editing Cancer stem cells(CSCs) are stem cells or progenitor cells that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer tissue. Cancer stem cells may generate cancer cells through self-renewal and differentiation. They are capable of repairing DNA, pumping out harmful substances from the cells, and staying in a quiescent state. In these situations, cancer stem cells do not respond to chemotherapeutic drugs, resulting in drug resistance. Therefore, eliminating cancer stem cells would be beneficial for overcoming drug resistance. To eradicate cancer stem cells, several types of functional drug liposomes have developed for specifically killing cancer stem cells, inducing the differentiation of cancer stem cells, modulating two apoptotic genes(pro-apoptotic and anti-apoptotic genes)(Biomaterials 2013, 34, 4452; Biomaterials 2014, 35, 5591; Biochem Pharmacol 2015, 95, 98), and more recently, inducing the cancer stem cells into normal cells by small molecule and crisper gene-editing reprogramming.Treatment of brain glioma by transporting across the BBB Invasive brain glioma is the most lethal type of cancer and is highly infiltrating. This leads to an extremely poor prognosis and makes complete surgical removal of the tumor virtually impossible. Non-penetration of therapeutic drugs across the blood–brain barrier(BBB), brain cancer stem cells(CSCs), and brain cancer vasculogenic mimicry(VM) results in relapse after surgical and radio therapy. The functional targeting chemotherapy enables the transporting drugs across the BBB, destroying VM channels, and eliminating CSCs and cancer cells in the brain, hence providing a new strategy for treating invasive brain glioma(Biomaterials 2014, 35, 5591; Biomaterials 2014, 35, 7610; Biomaterials 2014, 35, 5226; Adv Drug Deliv Rev 2017,115, 46).