ABSTRACT
In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The Fe3O4@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-Fe3O4@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-Fe3O4@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T2 magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-Fe3O4@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.
ABSTRACT
Objective: To prepare charge-reversal pH-sensitive nanoparticles loaded with curcumin (PCE/Cur NPs), and investigate the optimizing technology, physicochemical characterizations, and inhibitory effect on B16 cell. Methods: The β-carboxyl amidized cationic MPEG-PCL-PEI polymers (PCE) were negatively charged, which were prepared into the negative PCE/Cur NPs with pH dependence. When pH > 7, there was no charge-reversal. When pH < 6, the β-carboxyl amides were hydrolyzed rapidly into corresponding amines. As a result, PCE/Cur NPs became positively charged again. The obtained PCE/Cur NPs were characterized by detection of particle size, morphology study, drug loading, encapsulation efficiency, and release study. The effect of anti-migratory and anti-invasive actions of PCE/Cur NPs on B16 cell was investigated using MTT assays and wound healing test. Results: PCE/Cur NPs dependent on pH charge inversion were successfully prepared. The obtained PCE/Cur NPs were round, and the size was uniform, the adhesion was not found. The Results: showed that the prepared PCE/Cur NPs had the highest DL (8.0 ± 1.0)%, EE (90.0 ± 2.0)%, mean particle size of (80 ± 5) nm, and zeta potential of (-35 ± 5) mV. Within 48 h, the accumulative release rate was (69.2 ± 5.2)% (pH 7.4) and (71.2 ± 4.3)% (pH 5), respectively, and then PCE/Cur NPs released slowly. These Results: by MTT assay and wound healing assay indicated that PCE/Cur NPs not only inhibited the proliferation of B16 cells in a concentration- and time-dependent manner, but also can induce apoptosis. Conclusion: PCE/Cur NPs were prepared successfully, which might have great potential application in drug delivery system.
ABSTRACT
Objective:To investigate the application of CD44 receptor-targeted nanoparticles HACDDP-DOX in the treatment of breast cancer, and to clarify its inhibitory effect on allograft breast cancer in the mice. Methods:Hyaluronic acid(HA)was used to construct a breast cancer targeted nanoparticle via green synthesis approach,and its particle size,stability and doxorubicin release profile at different pH conditions were measured. Then the breast cancer models were constructed by inoculating 4T1 cells into the mouse mammary fat pad.The model mice were randomly divided into control group,DOX/CDDP group and HACDDP-DOX group according to the tumor volumes and the body weights.PBS,free drug DOX/CDDP and HACDDP-DOX were intravenously injected into the allograft breast cancer models on the 1st,5th and 9th days after the tumor volume reached about 80 mm3. The antitumor effect and biosafety of HACDDP-DOX were evaluated by detecting the tumor volume,mouse weight and immunohistopathology.Moreover,the biological distribution of HACDDP-DOX in the mice was studied by biofluorescence imaging.Results:The average particle size of HACDDP-DOX was(80.0 ± 17.4)nm,which was stable under pH 7.4.Under acidic condition,the particle size was increased and the DOX was effectively released. Compared with DOX/CDDP group,the body weight of the mice in HACDDP-DOX group was increased(P<0.05) and the tumor volume was decreased(P<0.05).The HE staining results showed that the liver of the mice in control group had tumor metastasis and the alveolar septum was widened.The tumor tissue of the mice in DOX/CDDP group and HACDDP-DOX group were all necrotic,while in HACDDP-DOX group the degree of necrosis was significantly higher than DOX/CDDP group.Compared with DOX/CDDP group,the activity of Caspase-3 in HACDDP-DOX group was significantly increased(P<0.01),while the Ki-67 activity was significantly decreased (P<0.01).The biofluorescence imaging showed that the nanoparticle HACDDP-DOX could accumulate to the tumor site by targeting,and effectively release the drug.Conclusion:HACDDP-DOX nanoparticles can effectively target the breast cancer cells,reduce the toxicity of chemotherapy drugs,and enhance the therapeutic effect of breast cancer.
ABSTRACT
Objective: To investigate the application of CD44 receptor-targeted nanoparticles HACDDP-DOX in the treatment of breast cancer, and to clarify its inhibitory effect on allograft breast cancer in the mice. Methods: Hyaluronic acid (HA) was used to construct a breast cancer targeted nanoparticle via green synthesis approach, and its particle size, stability and doxorubicin release profile at different pH conditions were measured. Then the breast cancer models were constructed by inoculating 4T1 cells into the mouse mammary fat pad. The model mice were randomly divided into control group, DOX/CDDP group and HACDDP-DOX group according to the tumor volumes and the body weights. PBS, free drug DOX/CDDP and HACDDP-DOX were intravenously injected into the allograft breast cancer models on the 1st, 5th and 9th days after the tumor volume reached about 80 mm5 The antitumor effect and biosafety of HACDDP-DOX were evaluated by detecting the tumor volume, mouse weight and immunohistopathology. Moreover, the biological distribution of HACDDP-DOX in the mice was studied by biofluorescence imaging. Results: The average particle size of HACDDP-DOX was (80.0 ± 17.4) nm, which was stable under pH 7.4. Under acidic condition, the particle size was increased and the DOX was effectively released. Compared with DOX/CDDP group, the body weight of the mice in HACDDP-DOX group was increased (P<0.05) and the tumor volume was decreased (P<0.05). The HE staining results showed that the liver of the mice in control group had tumor metastasis and the alveolar septum was widened. The tumor tissue of the mice in DOX/CDDP group and HACDDP-DOX group were all necrotic, while in HACDDP-DOX group the degree of necrosis was significantly higher than DOX/CDDP group. Compared with DOX/CDDP group, the activity of Caspase-3 in HACDDP-DOX group was significantly increased (P<0.01), while the Ki-67 activity was significantly decreased (P<0.01). The biofluorescence imaging showed that the nanoparticle HACDDPTXX could accumulate to the tumor site by targeting, and effectively release the drug. Conclusion: HACDDP-DOX nanoparticles can effectively target the breast cancer cells, reduce the toxicity of chemotherapy drugs, and enhance the therapeutic effect of breast cancer.