31P - Photothermal responsive, nucleolin-targeted bimetallic nano-vehicle delivered the combinational therapeutics for improved pancreatic cancer treatment

Background

Pancreatic cancer is the fourth most dominant disease leading the high mortality with a survival rate of 10%. Conventional therapeutics cause adverse effects as well as reoccurrence of pancreatic malignancy. Therefore, combination therapeutics including chemotherapy, photothermal, photodynamic, and immunotherapeutics has received great attention. The nanotechnological approaches are applied to develop the multifunctional nanocarrier to efficiently target the cancer cells without causing noticeable side effects. Therefore, herein we developed the multi-stimuli (pH, photothermal, and cancer cell receptor) responsive drug delivery system (DDS) for synergetic photothermal ablation of pancreatic cancer cells.

Methods

We synthesized the Au/Pd nanoparticles and conjugated them with 5-Fu using the CTAB. The 5fu-Au/Pd were loaded in CS through TPP ionic gelation. Then, apt was functionalized with 5fu-Au/Pd CS NPs by NHS and EDS covalent bonding method. The DDS (Apt-5fu-Au/Pd-CSNPs) were characterized for morphology, size, drug loading, entrapment, stimuli-responsive drug release, and photothermal conversion efficiency. Further, anticancer activity was evaluated in various molecular level cytotoxicity assays and animal tumor model experiments.

Results

DDS exhibited high drug loading and entrapment efficiency, and its size were exhibited <200 nm with a PDI of 0.23. The higher release of 5-Fu and Au/Pd were observed at the pH 5.4. This DDS exhibited the photothermal conversion efficiency of 28 %. The Apt-5fu-Au/Pd-CSNPs result in higher anticancer activity evidenced by the in-vitro cytotoxicity and animal experiments. The in vitro studies revealed that the treatment of Apt-5fu-Au/Pd-CSNPs triggers the cytotoxicity in the PANC-1 cells by regulating the MMP, ROS, apoptotic, and pro-apoptotic related proteins. The in-vivo studies reveal that the treatment of these DDS inhibited tumor proliferation and increase the mice's survival rate. And histopathological H & E staining studies confirmed the non-toxicity.

Conclusions

The present work delivered the novel nano DDS (Apt-5fu-Au/Pd-CSNPs) as an alternative to the conventional method of pancreatic cancer therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.