Advances in mesoporous silica-based nanocarriers for co-delivery and combination therapy against cancer

ABSTRACT

Introduction: Nanocarriers have emerged as a powerful alternative for cancer therapy. Indeed, they are promising candidates to tackle the acquired resistance of surviving cells against antiproliferative drugs – the so-called multidrug resistance (MDR) phenomenon – which has arisen as one of the major clinical issues of chemotherapy. Among nanocarriers, this review focuses on the recent approaches based on tailored mesoporous silica nanoparticles (MSNs) that could overcome this problem.

Areas covered: Herein we summarize the current efforts developed to provide MSN-based nanosystems of enhanced dual therapeutic action against diseased cells. This can be accomplished by three main approaches: i) increasing nanosystems’ killing capability towards particular cells by enhancing both recognition and specificity; ii) increasing the apoptotic effect throughout co-delivery of several drugs; or iii) combining drug delivery with apoptosis induced by physical methods.

Expert opinion: The development of multifunctional nanosystems able to exert the optimal therapeutic action through the minimal administration constitutes a major challenge in nanomedicine. Recent developments in advanced MSN-based platforms for drug delivery represent promising avenues in the management of MDR associated with cancer therapy. All strategies discussed in this manuscript demonstrate improvements against difficult-to-treat tumors.

KEYWORDS:

• Cancer treatment
• multidrug resistance
• co-delivery
• combination therapy
• dual targeting
• mesoporous silica nanoparticles

Article highlights

• Cancer cells tend to develop survival mechanisms against the usual chemotherapeutic employed for their treatment. Among known factors of enhanced survival there could be found antiapoptotic routes or drug efflux pumps that create this resistance to antitumor drugs.

• Nanocarriers and among them mesoporous silica nanoparticles are able to preferentially accumulate within the tumor mass and efficiently deliver toxic payloads; however, the delivery of one type of therapeutic compound usually does not solve the problem of acquired resistance, like raw drug administration. In spite of guidance has improved the selectivity and efficiency of the treatment towards diseased cells, there is still an issue when multidrug resistance appears.

• One recent attractive strategy to overcome the high survival ratio of multidrug resistance cancers consists in specifically targeting a concrete group of (diseased) cells by increasing the preferential uptake of nanotherapeutic and therefore reducing the overall dosage needed for the treatment.

• Another interesting approach is based on the maximization of the killing potential of carriers by including combinations of substances as cargoes able to exert simultaneous or synergistic action on more than one critical metabolic pathway.

• Furthermore a highly promising alternative to increase cell death could be also generated by dual combination of antiproliferative drugs with physical stimuli able to trigger additional apoptotic responses.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The authors acknowledge financial support from European Reseach Council [ERC-2015-AdG-694160 (VERDI)] and Ministerio de Economía y Competitividad [CSO2010-11384-E (Agening Network of Excellence), MAT2012-35556 and MAT2015-64831-R].