Related Experiment Video
Updated: Jul 4, 2026
Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
Microfluidic Synthesis of miR-10a Antisense Oligonucleotides-Loaded LNP Combined with Cisplatin for Colorectal Cancer
Shaorong Li1, Jinzhuai Li2, Hongmian Jiang1
1Medical Experimental Center, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, 530000, China.
Introduction:
To address the issue of insufficient sensitivity of the chemotherapeutic drug cisplatin in colorectal cancer (CRC), this study aimed to develop a miR-10a antisense oligonucleotide (AMO) system delivered by lipid nanoparticles (LNPs). The aim was to enhance the sensitivity and efficacy of cisplatin by targeting and inhibiting the expression of miR-10a in CRC.
Methods:
Through bioinformatics analysis, key miRNAs that are differentially expressed in colon cancer were identified. Then, by using the FDA-approved patisiran formulation and microfluidic technology, LNPs/miR10a- AMOs were constructed to target miR-10a. The transfection efficiency, anti-tumor effectiveness, and safety were evaluated through in vivo and in vitro experiments.
Results:
LNPs increased the transfection efficiency of AMOs by 2.3 times (p < 0.01). In HCT116 cells, miR- 10a expression was inhibited by 68.5%, and after combined treatment with cisplatin, the IC50 decreased from 8.7 μM to 5.0 μM (p < 0.001). Meanwhile, cell viability in normal THLE2 and HCoEpiC cells remained > 85%. In the xenograft model, the combined therapy achieved a 100.4% tumor growth inhibition compared to cisplatin monotherapy, with Ki67 expression decreased by 67.3%, and cleaved-caspase-3 expression increased by 3.1- fold (p<0.001). Histopathological analysis confirmed minimal organ toxicity. Mechanistically, miR-10a downregulation sensitized the tumor by activating the apoptotic pathway and inhibiting proliferation.
Discussion:
Our findings demonstrated that targeting miR-10a significantly enhanced the sensitivity of tumor cells to cisplatin, providing a novel strategic approach to overcome chemoresistance. Compared to existing studies, the innovation of this work lies in employing an FDA-approved LNP formulation, substantially improving the feasibility for clinical translation. Furthermore, the application of microfluidic technology ensured reproducible nanoparticle preparation, offering distinct advantages over conventional methods in terms of industrial applicability. However, this study has involved certain limitations; the animal models utilized could not fully recapitulate the complexity of the human tumor microenvironment, and the precise molecular mechanisms regulated by miR-10a warrant further investigation.
Conclusion:
LNPs/miR-10a-AMOs can efficiently deliver AMOs and represent a potential strategy for treating CRC. By enhancing the sensitivity of tumors to cisplatin, this system improved the therapeutic effect while ensuring the safety of normal cells. This provides a new strategy with translational potential for the precise treatment of CRC.
Insights
This study developed lipid nanoparticles (LNPs) to deliver miR-10a antisense oligonucleotides (AMOs), enhancing cisplatin sensitivity in colorectal cancer (CRC). The novel system improved treatment efficacy and safety, offering a promising strategy for CRC therapy.
Area of Science:
- Biomedical Engineering
- Molecular Oncology
- Drug Delivery Systems
Background:
- Colorectal cancer (CRC) exhibits insufficient sensitivity to cisplatin chemotherapy.
- Targeting microRNA-10a (miR-10a) is a potential strategy to overcome chemoresistance.
- Antisense oligonucleotide (AMO) systems offer a method for gene silencing.
Purpose of the Study:
- To develop a novel drug delivery system using lipid nanoparticles (LNPs) to deliver miR-10a antisense oligonucleotides (AMOs).
- To enhance the sensitivity and efficacy of cisplatin chemotherapy in colorectal cancer (CRC) by inhibiting miR-10a expression.
- To evaluate the anti-tumor effectiveness and safety of the LNP/miR-10a-AMO system in combination with cisplatin.
Main Methods:
- Bioinformatics analysis to identify key differentially expressed miRNAs in colon cancer.
- Construction of LNPs/miR-10a-AMOs using an FDA-approved formulation and microfluidic technology.
- In vitro and in vivo evaluation of transfection efficiency, anti-tumor activity, and safety.
Main Results:
- LNPs significantly increased AMO transfection efficiency (2.3-fold).
- Combined therapy with LNPs/miR-10a-AMOs and cisplatin reduced IC50 by 43% in HCT116 cells, with minimal toxicity to normal cells.
- In vivo studies showed 100.4% tumor growth inhibition, decreased proliferation markers (Ki67), and increased apoptosis markers (cleaved-caspase-3) with minimal organ toxicity.
Conclusions:
- The developed LNPs/miR-10a-AMOs system effectively delivers AMOs and enhances cisplatin sensitivity in CRC.
- This approach presents a novel, safe, and potentially translatable strategy for precise colorectal cancer treatment.
- The use of an FDA-approved LNP formulation and microfluidic technology enhances clinical feasibility and industrial applicability.
