pH-Responsible fluorescent carbon nanoparticles for tumor selective theranostics via pH-turn on/off fluorescence and photothermal effect in vivo and in vitro

Nanoscale ◽  
2018 ◽  
Vol 10 (5) ◽  
pp. 2512-2523 ◽  
Author(s):  
Eun Bi Kang ◽  
Jung Eun Lee ◽  
Zihnil Adha Islamy Mazrad ◽  
Insik In ◽  
Ji Hoon Jeong ◽  
...  

Here we designed the functionalized FNP as “switch-on” fluorescence probes to sense intracellular cancer cells and controllable photothermal therapy (PTT) in vivo and in vitro.

2021 ◽  
Author(s):  
Fengji Li ◽  
Yanling Yan ◽  
Yanan Wang ◽  
Yaru Fan ◽  
Huiru Zou ◽  
...  

Abstract Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumours in the oral and maxillofacial regions and is highly malignant and prone to recur despite the development of various effective treatments, including surgery and chemoradiotherapy. Actually, it is difficult to ensure the complete elimination of tumour cells, and maxillofacial bone defects caused by surgery are hard to heal by themselves. In addition, chemoradiotherapy can bring serious side effects. Therefore, it is imperative to develop a postoperative therapy to kill residual squamous cancer cells and repair bone defects without any side effects. Here, we prepared a three-dimensional (3D) scaffold by a 3D printing technique and freeze-drying method, which contained collagen, silk and hydroxyapatite (CSH) and was functionalized with MXene nanosheets (M-CSH). The considerable photothermal effect with long-term stability can significantly kill squamous CAL-27 cancer cells in vitro and inhibit tumour growth in vivo, increasing the probability of the M-CSH scaffold being applied in the photothermal therapy of OSCC. Moreover, the cell proliferation- and osteogenic-related protein expression of mouse embryonic osteogenic precursors (MC3T3-E1) indicated excellent biocompatibility and osteogenic activity of M-CSH scaffolds. The good compression modulus (52.83 ± 2.25 kPa) and in vivo bone formation performance made it possible to be used as reconstructive materials for bone defects. This scaffold is likely promising in future tissue engineering, especially for the multifunctional treatment of maxillofacial tumours.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qing-Hai Xia ◽  
Cui-Tao Lu ◽  
Meng-Qi Tong ◽  
Meng Yue ◽  
Rui Chen ◽  
...  

Hepatocellular carcinoma is a malignant tumor with high morbidity and mortality, a highly effective treatment with low side effects and tolerance is needed. Photothermal immunotherapy is a promising treatment combining photothermal therapy (PTT) and immunotherapy. PTT induces the release of tumor-associated antigens by ablating tumor and Ganoderma lucidum polysaccharides (GLP) enhance the antitumor immunity. Results showed that Indocyanine Green (ICG) was successfully encapsulated into SF-Gel. ICG could convert light to heat and SF-Gel accelerates the photothermal effect in vitro and in vivo. PTT based on ICG/ICG-SF-Gel inhibited the growth of primary and distal tumors, GLP enhanced the inhibitory efficacy. ICG/ICG-SF-Gel-based PTT and GLP immunotherapy improved the survival time. ICG/ICG-SF-Gel-based PTT induces tumor necrosis and GLP enhanced the photothermal efficacy. ICG/ICG-SF-Gel-based PTT inhibited cell proliferation and angiogenesis, induced cell apoptosis, enhanced cellular immunity, and GLP enhanced these effects. In conclusion, GLP could enhance the abscopal effect of PTT in Hepatoma-bearing mice.


2019 ◽  
Vol 20 (5) ◽  
pp. 1042 ◽  
Author(s):  
Apriliana Cahya Khayrani ◽  
Hafizah Mahmud ◽  
Aung Ko Ko Oo ◽  
Maram H. Zahra ◽  
Miharu Oze ◽  
...  

Paclitaxel (PTX) is one of the front-line drugs approved for the treatment of ovarian cancer. However, the application of PTX is limited due to the significant hydrophobicity and poor pharmacokinetics. We previously reported target-directed liposomes carrying tumor-selective conjugated antibody and encapsulated glycosylated PTX (gPTX-L) which successfully overcome the PTX limitation. The tubulin stabilizing activity of gPTX was equivalent to that of PTX while the cytotoxic activity of gPTX was reduced. In human ovarian cancer cell lines, SK-OV-3 and OVK18, the concentration at which cell growth was inhibited by 50% (IC50) for gPTX range from 15–20 nM, which was sensitive enough to address gPTX-L with tumor-selective antibody coupling for ovarian cancer therapy. The cell membrane receptor CD44 is associated with cancer progression and has been recognized as a cancer stem cell marker including ovarian cancer, becoming a suitable candidate to be targeted by gPTX-L therapy. In this study, gPTX-loading liposomes conjugated with anti-CD44 antibody (gPTX-IL) were assessed for the efficacy of targeting CD44-positive ovarian cancer cells. We successfully encapsulated gPTX into liposomes with the loading efficiency (LE) more than 80% in both of gPTX-L and gPTX-IL with a diameter of approximately 100 nm with efficacy of enhanced cytotoxicity in vitro and of convenient treatment in vivo. As the result, gPTX-IL efficiently suppressed tumor growth in vivo. Therefore gPTX-IL could be a promising formulation for effective ovarian cancer therapies.


2021 ◽  
Author(s):  
Lin Zhang ◽  
Ling Li ◽  
Xia Wang ◽  
Jing Dai ◽  
Linglli Zhou ◽  
...  

PROteolysis TArgeting Chimeras (PROTACs) induce targeted protein degradation by hijacking the intracellular ubiquitin proteasome system, thus emerging as a new strategy for drug development. However, although PROTACs are highly efficient for protein degradation, most PROTACs generated lack cell-type selectivity, resulting in potential off-tissue, on-target toxicity. To address this drawback, we herein developed an aptamer-based PROTAC ZL216 using aptamer AS1411 as a targeting ligand for nucleolin, and it showed both excellent serum stability and water solubility. Based on the differential expression of nucleolin on the cell surface, ZL216 can specifically bind to and internalize into breast cancer cells, but not normal breast cells. Furthermore, we revealed that ZL216 promoted the formation of a nucleolin-ZL216-VHL ternary complex in breast cancer cells and potently induced the degradation of nucleolin in vitro and in vivo, thereby inhibiting the proliferation and migration of breast cancer cells. These studies demonstrated the potential of utilizing aptamers to construct PROTACs to achieve the selective degradation of targeted protein in tumor cells and provided a promising strategy for the development of tumor-selective PROTACs.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhanxia Zhang ◽  
Junqian Zhang ◽  
Jianhui Tian ◽  
Hegen Li

AbstractKnocking down the oncogene ROC1 with siRNA inhibits the proliferation of cancer cells by suppressing the Neddylation pathway. However, methods for delivering siRNA in vivo to induce this high anticancer activity with low potential side effects are urgently needed. Herein, a folic acid (FA)-modified polydopamine (PDA) nanomedicine used in photothermal therapy was designed for siRNA delivery. The designed nanovector can undergo photothermal conversion with good biocompatibility. Importantly, this genetic nanomedicine was selectively delivered to liver cancer cells by FA through receptor-mediated endocytosis. Subsequently, the siRNA cargo was released from the PDA nanomedicine into the tumor microenvironment by controlled release triggered by pH. More importantly, the genetic nanomedicine not only inhibited liver cancer cell proliferation but also promoted liver cell apoptosis by slowing ROC1 activity, suppressing the Neddylation pathway, enabling the accumulation of apototic factor ATF4 and DNA damage factor P-H2AX. Combined with photothermal therapy, this genetic nanomedicine showed superior inhibition of the growth of liver cancer in vitro and in vivo. Taken together, the results indicate that this biodegradable nanomedicine exhibits good target recognition, an effective pH response, application potential for genetic therapy, photothermal imaging and treatment of liver cancer. Therefore, this work contributes to the design of a multifunctional nanoplatform that combines genetic therapy and photothermal therapy for the treatment of liver cancer.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 675
Author(s):  
Chun Chu ◽  
Zhihong Bao ◽  
Meng Sun ◽  
Xiaowei Wang ◽  
Hongyan Zhang ◽  
...  

The combination of chemotherapy and phototherapy has attracted increasing attention for cancer treatment in recent years. In the current study, porous PdPt bimetallic nanoparticles (NPs) were synthesized and used as delivery carriers for the anti-cancer drug doxorubicin (DOX). DOX@PdPt NPs were modified with thiol functionalized hyaluronic acid (HA-SH) to generate DOX@PdPt@HA NPs with an average size of 105.2 ± 6.7 nm. Characterization and in vivo and in vitro assessment of anti-tumor effects of DOX@PdPt@HA NPs were further performed. The prepared DOX@PdPt@HA NPs presented a high photothermal conversion efficiency of 49.1% under the irradiation of a single 808 nm near-infrared (NIR) laser. Moreover, NIR laser irradiation-induced photothermal effect triggered the release of DOX from DOX@PdPt@HA NPs. The combined chemo-photothermal treatment of NIR-irradiated DOX@PdPt@HA NPs exerted a stronger inhibitory effect on cell viability than that of DOX or NIR-irradiated PdPt@HA NPs in mouse mammary carcinoma 4T1 cells in vitro. Further, the in vivo combination therapy, which used NIR-irradiated DOX@PdPt@HA NPs in a mouse tumor model established by subcutaneous inoculation of 4T1 cells, was demonstrated to achieve a remarkable tumor-growth inhibition in comparison with chemotherapy or photothermal therapy alone. Results of immunohistochemical staining for caspase-3 and Ki-67 indicated the increased apoptosis and decreased proliferation of tumor cells contributed to the anti-tumor effect of chemo-photothermal treatment. In addition, DOX@PdPt@HA NPs induced negligible toxicity in vivo. Hence, the developed nanoplatform demonstrates great potential for applications in photothermal therapy, drug delivery and controlled release.


2018 ◽  
Vol 318 (3) ◽  
pp. 1913-1921 ◽  
Author(s):  
Abraham González-Ruíz ◽  
Guillermina Ferro-Flores ◽  
Nallely Jiménez-Mancilla ◽  
Alondra Escudero-Castellanos ◽  
Blanca Ocampo-García ◽  
...  

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
RuiMei Jin ◽  
Jie Yang ◽  
DongHui Zhao ◽  
XiaoLin Hou ◽  
ChaoQing Li ◽  
...  

Abstract Background Combined therapy has demonstrated to be an effective strategy for cancer therapy. Herein, an injectable hydrogel based on the genetically engineered polypeptide and hollow gold nanoshells (HAuNS) has been developed for chemo-photothermal therapy of HepG2 tumor. Methods PC10A/DOX/HAuNS nanogel was prepared with layer-by-layer through the adsorption of DOX and PC10A successively. DOX with positive charge and PC10A with negative charge were coated step by step onto the surface of negatively charged HAuNS. The multifunctional hydrogel PC10A/DOX/HAuNS were prepared via dissolving hybrid PC10A/DOX/HAuNS nanogel in polypeptide PC10A. Chemotherapy drug DOX in the PC10A/DOX/HAuNS hydrogel was absorbed on the HAuNS and directly embedded in the PC10A hydrogel, which contributes to sequentially release of the drug. Specifically, DOX adsorbed on the HAuNS could be released slowly for sustainable chemotherapy. Results The PC10A/DOX/HAuNS hydrogel could pass 26-gauge needle without clogging, indicating that it is injectable. In addition, the PC10A/DOX/HAuNS hydrogel possessed outstanding photothermal effect and photothermal stability. In both in vitro cell and in vivo tumor-bearing mice experiments, a remarkably enhance tumor inhibition was observed by the combined therapy of chemo-photothermal therapy compared with photothermal therapy or chemotherapy alone. Conclusions The combined chemotherapy and photothermal therapy of PC10A/DOX/HAuNS hydrogels could significantly improve the therapeutic effect. Therefore, the multifunctional hydrogel PC10A/DOX/HAuNS is promising to provide a new strategy for sustained chemo-photothermal therapy.


Sign in / Sign up

Export Citation Format

Share Document