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Published on: June 13, 2014
Amorphous calcium phosphate nanoparticles could function as a novel cancer therapeutic agent by employing a suitable
Milad Pourbaghi-Masouleh, Vahid Hosseini1
1Department of Health Science and Technology, Laboratory of Applied Mechanobiology, ETH, Zürich 8093, Switzerland. vahid.hosseini@hest.ethz.ch.
Abstract:
Employment of nanovehicular system for delivering apoptogenic agent to cancer cells for inducing apoptosis has widely been investigated. Loading efficacy and controlled release of the agents are of the inseparable obstacles that hamper the efforts in reaching an efficacious targeted cancer therapy method. When the carrier itself is apoptogenic, then there is no need to load the carrier with apoptogenic agent and just delivering of the particle to the specific location matters. Hence, we hypothesize that amorphous calcium phosphate nanoparticle (ACPN) is a potent candidate for apoptosis induction, although encapsulation in liposome shell, and surface decoration with targeting ligand (TL), and cell-penetrating peptide (CPP) plays a pivotal role in the employment of this agent. It is well understood that elevation in cytosolic Ca2+ ([Ca2+]c) would result in the induction of apoptosis. ACPN has the potential to cause imbalance in this medium by elevating [Ca2+]c. Owning to the fact that the nanoparticles should be delivered into cytosol, it is necessary to trap them in a liposomal shell for evading endocytosis. It was demonstrated that employment of the trans-activator of transcription (TAT) as CPP eminently enhances the efficacy of endosomal escape; therefore, the platform is designed in a way that TAT is positioned on the surface of the liposome. Due to the fact that the apoptosis should be induced in sole cancer cells, Folate as TL is also attached on the surface of the liposome. This hypothesis heralds the new generation of chemotherapeutic agents and platforms which could have less side effect than the most common ones, in addition to other advantages they have.
Insights
Amorphous calcium phosphate nanoparticles (ACPNs) can induce cancer cell apoptosis. Encapsulating ACPNs in liposomes with targeting ligands and cell-penetrating peptides enhances their delivery and efficacy for targeted cancer therapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Targeted cancer therapy faces challenges with loading efficacy and controlled release of apoptogenic agents.
- Developing novel nanocarriers that are inherently apoptogenic simplifies drug delivery.
- Amorphous calcium phosphate nanoparticle (ACPN) is proposed as a potential apoptogenic agent.
Purpose of the Study:
- To investigate the potential of amorphous calcium phosphate nanoparticle (ACPN) as a carrier for inducing apoptosis in cancer cells.
- To enhance ACPN delivery and efficacy through encapsulation in liposomes decorated with targeting ligands (TL) and cell-penetrating peptides (CPP).
Main Methods:
- Designing a nanovehicular system with ACPN as the core agent.
- Encapsulating ACPN within a liposome shell to facilitate cytosolic delivery and evade endocytosis.
- Decorating the liposome surface with Folate as a targeting ligand for cancer cells.
- Utilizing the trans-activator of transcription (TAT) as a cell-penetrating peptide (CPP) to enhance endosomal escape.
Main Results:
- ACPNs have the potential to induce apoptosis by elevating cytosolic calcium ion concentration ([Ca2+]c).
- Liposomal encapsulation and surface modification with TAT and Folate are crucial for effective delivery and targeting.
- This approach aims to overcome limitations of current nanocarrier systems in cancer therapy.
Conclusions:
- The proposed nanovehicular system offers a novel strategy for targeted cancer therapy.
- This approach may lead to a new generation of chemotherapeutic agents with potentially fewer side effects.
- Further research is warranted to validate the efficacy and safety of this ACPN-based system.
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