Doxorubicin Intercalated Co-Al Layered Double Hydroxide Nanocarrier With pH-Responsive Controlled Release and
Swapan Maity1, Akshita Upreti2, Souvik Chowdhury1
1School of Materials Science and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India.
Abstract:
Clinical oncology grapples with persistent challenges, particularly the rapid onset of tumor resistance and the systemic limitations of conventional chemotherapeutics such as doxorubicin (Dox). Despite its potency, Dox suffers from poor solubility, non-specific distribution, and severe toxicity, often compromising therapeutic efficacy. Addressing these obstacles, this study explores cobalt-aluminium layered double hydroxides (Co-Al LDHs) as smart nanocarriers for targeted melanoma therapy. Capitalizing on their tunable structure, high drug-loading capacity, and biocompatibility, Co-Al LDHs facilitate enhanced encapsulation, sustained release, and selective tumor accumulation of Dox. Density Functional Theory (DFT) analyses confirm robust molecular interactions between Dox and the LDH matrix, ensuring structural stability and favorable energetics for drug delivery. In vitro assays reveal significant cytotoxicity (≈80%) against melanoma cells and with minimal toxicity (≈8%) to normal muscle cells. Furthermore, in vivo evaluations using luciferase-tagged B16-F10 melanoma models demonstrate pronounced tumor inhibition and excellent systemic biocompatibility. Augmented by machine learning-guided force field modelling, this platform also offers a predictive framework for engineering next-generation nanotherapeutics. Together, these findings position Co-Al LDHs as a promising frontier in nanomedicine, merging targeted delivery, controlled release, and computational precision to overcome current therapeutic barriers in melanoma treatment and beyond.
Insights
Cobalt-aluminium layered double hydroxides (Co-Al LDHs) effectively deliver doxorubicin (Dox) to melanoma tumors, enhancing efficacy and reducing toxicity. This nanomedicine platform shows promise for overcoming drug resistance and improving cancer therapy.
Area of Science:
- Nanomedicine
- Materials Science
- Oncology
Background:
- Conventional chemotherapy faces challenges like tumor resistance, poor drug solubility, and systemic toxicity.
- Doxorubicin (Dox) exhibits limitations including poor solubility, non-specific distribution, and severe side effects.
- Targeted drug delivery systems are needed to improve therapeutic efficacy and reduce toxicity in cancer treatment.
Purpose of the Study:
- To investigate cobalt-aluminium layered double hydroxides (Co-Al LDHs) as nanocarriers for targeted melanoma therapy.
- To evaluate the encapsulation, release, and delivery capabilities of Dox-loaded Co-Al LDHs.
- To assess the efficacy and biocompatibility of Co-Al LDHs for melanoma treatment.
Main Methods:
- Synthesis and characterization of cobalt-aluminium layered double hydroxides (Co-Al LDHs).
- Loading of doxorubicin (Dox) into Co-Al LDHs and assessment of encapsulation efficiency and release kinetics.
- In vitro cytotoxicity assays on melanoma and normal cells.
- In vivo studies using a melanoma tumor model in mice.
- Density Functional Theory (DFT) and machine learning-guided force field modeling for interaction analysis.
Main Results:
- Co-Al LDHs demonstrated high drug-loading capacity and sustained release of Dox.
- In vitro studies showed significant cytotoxicity against melanoma cells (≈80%) with minimal toxicity to normal cells (≈8%).
- In vivo evaluations confirmed pronounced tumor inhibition and excellent systemic biocompatibility in a melanoma model.
- DFT and ML modeling supported the stability and favorable energetics of Dox-LDH interactions.
Conclusions:
- Co-Al LDHs serve as effective nanocarriers for targeted doxorubicin delivery in melanoma.
- This nanomedicine approach enhances therapeutic efficacy while minimizing systemic toxicity.
- The combination of experimental and computational methods provides a framework for developing advanced nanotherapeutics for cancer treatment.
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