Abstract
The paramount discovery of passive accumulation of nanoparticles in tumoral tissues triggered the development of a wide number of different nanoparticles capable of transporting therapeutic agents to tumoral tissues in a controlled and selective way. These nanocarriers have been endowed with important capacities such as stimuli-responsive properties, targeting abilities, or the capacity to be monitored by imaging techniques. However, after decades of intense research efforts, only a few nanomedicines have reached the market. The reasons for this disappointing outcome are varied, from the high tumor-type dependence of enhanced permeation and retention (EPR) effect to the poor penetration capacity of nanocarriers within the cancerous tissue, among others. The rapid nanoparticle clearance by immune cells, considered another important barrier, which compromises the efficacy of nanomedicines, would become an important ally in the fight against cancer. In the last years, the fine-tuned ability of immune cells to recognize and engulf nanoparticles have been exploited to deliver immunoregulating agents to specific immune cell populations selectively. In this work, the recent advances carried out in the development of nanocarriers capable of operating with immune and tumoral cells in order to orchestrate an efficient antitumoral response will be presented. The combination of nanoparticles and immunotherapy would deliver powerful weapons to the clinicians that offer safer and more efficient antitumoral treatments for the patients.
Highlights
The paramount discovery of the passive accumulation of nanoparticles in solid tumors carried out by Maeda and Matsumura a few decades ago [1] opened a new way to treat these malignancies.This phenomena, called enhanced permeation and retention (EPR) effect, is due to the high porosity of the tumoral blood vessels which allows the extravasation of the nanoparticles once they arrive at the diseased tissue in combination with impaired lymphatic drainage within the tumor, that enhances the accumulation of the nanomedicines in the malignancy [2]
Thanks to the creativity and hard work of the scientific community, a myriad of different nanocarriers endowed with remarkable properties have been reported
These nanocarriers can be engineered with the capacity to release their cargo on-demand, ability to recognize their target cell, and even certain organelles inside them and can be monitored in real-time during their journey through the patient
Summary
The paramount discovery of the passive accumulation of nanoparticles in solid tumors carried out by Maeda and Matsumura a few decades ago [1] opened a new way to treat these malignancies. This property is usually achieved by the use of active targeting strategies, which consist of the attachment on the particle surface of small molecules, proteins, or oligonucleotide chains, known as targeting groups, which binds with certain membrane receptors overexpressed by the tumoral cells [16] Nanocarriers decorated with these targeting moieties have achieved excellent selectivity to deliver therapeutic agents to tumoral cells [17] and to provide information about the cancerous tissue by different imaging techniques [18]. Nanoparticles can be loaded with different drugs to induce several effects at the same time, such as tumoral cell elimination that enhances tumoral antigen release and immunostimulating agents, which induce immune cell maturation Another approach is to use nanoparticles to remove the immunosuppressive environment, usually present in tumors. This review will be focused on the application of these tumor-targeted nanoparticles capable of triggering efficient and selective antitumoral responses
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