The topic is Biointerfacing polymeric microcapsules for In vivo near

The topic is Biointerfacing polymeric microcapsules for In vivo near-infrared light-triggered drug release.Written by Shao Jingxin The First part:Abstract To seek safe and effective water-soluble drug carrier, the group present a novel drug delivery system based on biointerfaceing hollow polymeric microcapsules for effectively encapsulating water-soluble antitumor drug and gold nanorods (GNRs) fuctionalization for triggeredly releasing therapeutic drugs on-demand using low power near-infrared (NIR) radiation. The surface of polymeric microcapsules is covered with fluidic lipid bilayers to decrease thepermeability of the wall of polymeric capsules. In vivo antitumor tests demonstrate that this microcapsule has the effective ability of inhibiting tumor growth and preventing metastases. Realtime in vivo fluorescence imaging results confirm that capsules can be excreted gradually from the animal body which in turn demostrates the biocompatibility and biodegradation of these biointerfacing GNRs-microcapsules. This intelligent system provides a novel anticancer platform with the advantages of controled release, biological friendliness and credible biosafety. The Second part:introduction A novel NIR-responsive microcapsule with controlled release function by embedding gold nanorod (GNRs) into a wall of microcapsules was prepared as illustrated in Fig. 1A. Microcapsules are synthesized by Lb L assembly of biocompatible polysaccharide chitosan and alginate on the surface of silica microparticles following by the removal of sacrifice templates. Usually, small molecular hydrophilic drugs are difficult to be encapsulated since the larger pore sizes of these microcapsules. Thus, forming fluidic natural lipid bilayers on the surface of microcapsules through vesicle fusion method can effectively seal hydrophilic anti-cancer drugs. Furthermore, GNRs embedded in the wall of capsules were used to control drug release by transforming absorbed light energy into heat and thus disturbing the integrity of both lipid membrane and the wall of capsules. In order to evaluate the anti-tumor therapy of this controlled release system, in vivo test was conducted as shown in Fig. 1B. Drug loading GNRs-capsules were intratumoral injected into tumor-bearing mouse, followed by NIR irradiation. In vitro and in vivo experiments demonstrate the high efficient antitumor activity of this controlled release system. The third part:Results and Discussion 1.Fabrication and characterization of GNRs-microcapsules Fig. 2 (A) SEM image of GNRs. The inset is TEM image (B) SEM image of GNRs-microcapsules. The insert is the TEM image of GNRs-microcapsule. (C) UV-Vis-NIRextinction spectra of GNRs and GNRs-capsules. (D) Theoretical stimulation of temperature distribution of GNRs irradiated with a laser power .Inset image is corresponding TEM image of GNRs distribution on the capsule with higher magnification. From A and B,It can be demonstrated that GNRs were successfully assembled into the wall of microcapsules. NIR light (650-900 nm) damages skin and tissue minimally and became a hot topic for anticancer therapy .As-prepared GNRs has maximum absorption wavelength (836 nm) in near-infrared region Justas(Fig. 2C). GNRs were selected as a component of polyelectrolyte multilayer films for gathering NIR light responsive property.For FIG2DIt shows that laser-induced temperature increment localized in a small area around gold nanorod (nanometer size), which is significantly smaller than the cells (micrometer size), thus the photothermal effect towards cells can be ignored. 2. Encapsulating DOX into GNRs-microcapsules (A) CLSM Image of lipid modified microcapsules. (B) CLSM image of DOX loading microcapsules。The fluorescent intensity profile shows that biointerfacing GNRs-microcapsules were successfully filled with DOX. (C) Release profiles of DOX in GNRs-microcapsules and in lipid modified microcapsules at 37 ℃with or without NIR laser illumination. The release of lipid bilayers modified capsule was remarkably slow,herefore, lipid bilayers significantly reduce the permeability of the wall of microcapsules.After exposed to the NIR laser, 80% of DOX from lipid modified capsules was release. It directly proved that the release of encapsulated drug can be remotely controlled by NIR laser. 3. NIR controlled release of DOX from GNRs-microcapsules in vitro Fig. 4 Controlled release of anticancer drug DOX from GNRs-microcapsules by means of the NIR laser and characterized by TP-CLSM. (A) MCF-7 cells incubated with GNRs-microcapsules filled with DOX under NIR irradiation(B) MCF-7 cells incubated with GNRs-microcapsules without DOX loading under NIR irradiation.(C) MCF-7 cells incubated with DOX loaded microcapsules under the same laser irradiation condition. (D) MCF-7 cells directly irradiated with NIR laser For A group,encapsulated DOX was instantaneously released and cellbegun to necrosis by DOX effect subsequently.For B,C and D group,No obvious cell necrosis was observed.The above results conclude that NIR light responsive GNRs-capsules can be opened without killing tumor cells, laser only have the effect of drug controlled release under this condition. 4. Biodistribution of GNRs-microcapsules in vivo Fig. 5 (A) In vivo fluorescence images of the 4T1 tumor bearing nude mouse after treatment with Cy7 labelled GNRs-microcapsules. (B) In vivo fluorescence image of the 4T1 tumor bearing nude mousewith PBS injection.(C)Biodistribution of GNRs-microcapsules in the organ and tumor tissues harvested 24 h after intratumoral injection. As shown in Fig. 5A, at 1h post-injection, it is obvious that the capsules were mainly distributed around the tumor site. As shown in Fig. 5c, the content of Au