Self-Assembly of Drug-Loaded Liposomes on Genetically Engineered Target-Recognizing M13 Phage: A Novel Nanocarrier for Targeted Drug Delivery
Self-Assembly of Drug-Loaded Liposomes on Genetically Engineered Target-Recognizing M13 Phage: A Novel Nanocarrier for Targeted Drug Delivery
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DOI：
10.1002/smll.200801902
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发表时间：
2009-09-04
期刊：
影响因子：
13.3
通讯作者：
Mao, Chuanbin
中科院分区：
文献类型：
--
作者：
Ngweniform, Pascaline;Abbineni, Gopal;Mao, Chuanbin
Liposomes have been a center of research for many years due to their numerous applications in chemistry, biology, medicine, and nanotechnology.[1, 2] They can be used to entrap materials such as drugs either within the central aqueous compartment if they are water soluble, or within the hydrophobic domain of the lipid bilayer if they are oil soluble.[3, 4] In addition, their surface can be modified to realize targeted delivery.[1] For example, in biomedicine, liposomes are used as vehicles to deliver drugs and genes to specific parts of the body. When used in the delivery of certain anticancer drugs, liposomes help to shield healthy cells from the drug toxicity and prevent concentration in vulnerable tissues. In addition, the liposomes allow much smaller doses of drug to be used, thus reducing the side effects of that drug. On the other hand, zinc phthalocyanine (ZnPc) is a potential drug that is being tested as a photosensitizer for photodynamic therapy (PDT).[5] PDT involves the systemic administration of a photosensitizer followed by illumination with light of an appropriate wavelength, which results in the formation of singlet oxygen (1O2) for destroying cancer cells.[6] ZnPc has a high absorption coefficient at 650–700 nm with optimal tissue penetration.[7] It has a long lifetime in the triplet excited state, thus resulting in the highly efficient production of 1O2 which is the main cytotoxic species in PDT.[7, 8] However, it is insoluble in water and must be incorporated into unilamellar liposomes (Figure 1a). The main drawback of liposomes is their instability in biological media, as well as their sensitivity to many external parameters, such as temperature or osmotic pressure. This instability problem affects the application of liposomes in drug/gene delivery and PDT. Attempts have been made to stabilize liposomes by adsorbing some hydrophobic and hydrophilic polymers on them.[9, 10] This method may not be compatible with biological systems because some polymers may be toxic. M13 phage (Figure 1b and Figure S1 in the Supporting Information) is a rodlike virus (% 1-mm-long and% 7-nm-wide for wild type) that specifically infects bacteria and is nontoxic to human beings.[11] Its sidewall is self-assembled from% 2700 copies of the highly ordered, genetically modifiable major coat protein (called gP8). The two ends of the rodlike virus (Figures 1b and S1) can be engineered to identify and display a peptide that can recognize a specific target (eg, cells, tissues, or organs) through a technique called phage display.[12–14] Recent human clinical trials discovered that the rodlike phage will not induce obvious toxicity and immune response in human beings.[15] Recent animal studies also suggest that the rodlike phage can carry drugs that are chemically tethered to
