Nanophotosensitizers for cancer therapy: a promising technology?

Abstract

Photodynamic therapy (PDT) has been clinically applied to cure various diseases including cancer. Indeed, photophrin (porfimer sodium, Axcan Pharma, Montreal, Canada), a heterogenous mixture of porphyrins, was the first photosensitizer (PS) approved for the treatment of human bladder cancer in 1993 in Canada. Over the past 10 years the use of PDT in the treatment of benign and malignant lesions has increased dramatically. However, PDT is still considered as an adjuvant strategy due to its limitations, primarily including low tissue penetration by light and inaccurate lesion selectivity by the PSs. To overcome this scenario, new technologies and approaches including nanotechnology have been incorporated into the concept of PS formulations as PS delivery systems, as PSs per se or as energy transducers. The ideal nanophotosensitizer (NPS) for cancer therapy should possess the following characteristics: biocompatibility and biodegradability without toxicity, stability in physiological conditions, tumor specific targeting, strong near infrared absorption for efficient and sufficient light absorbance and large singlet oxygen quantum yield for PDT. To fulfill these requirements, several nanoscale delivery platforms and materials have been developed. In this review we will focus on the state of the art of nanotechnology contributions to the optimization of PDT as a therapeutic alternative to fight against cancer. For this purpose we will start from the basic concepts of PDT, discuss the versatility in terms of NPS formulations and how to tackle the deficiencies of the current therapy. We also give our critical view and suggest recommendations for improving future research on this area.

Fundamentals and applications of metal nanoparticle- enhanced singlet oxygen generation for improved cancer photodynamic therapy

“…Compared to the free molecular conventional PSs, nano-formulations of PSs impart certain unique and improved properties that make them more potent for PDT applications. First of all, nanomaterials act as a stable and potent drug delivery carrier which generally overcomes the shortcomings of free molecular PSs like hydrophobicity, aggregations, and low tumor cell/tissue specificity, and further permits higher loading of PSs allowing controlled delivery and accumulation in tumor mass in higher concentrations (Zhang et al, 2016;dos Santos et al, 2021;Yan et al, 2020). The smaller size and stability of NPs prolongs the circulation of PSs in the system, enables passive targeting and higher accumulation of PSs in the tumor mass by enhanced permeation and retention (EPR) effect, whereby the leaky and improperly generated tumor vasculatures allow enhanced penetration of circulating NPs in tumor tissues.…”

Nanoparticle-Mediated Delivery Systems in Photodynamic Therapy of Colorectal Cancer

“…Conventional PDT, like other traditional therapies, has also been associated with recurrence and resistance [69]. The possible mechanism of resistance to PDT may be attributed to several properties, such as inherent tumour heterogeneity and drug efflux [69,70]. Nonetheless, studies have reported that a cancer cell population that is resistant to chemotherapeutic treatment, to some extent, can be slightly more susceptible to PDT [70].…”

“…The possible mechanism of resistance to PDT may be attributed to several properties, such as inherent tumour heterogeneity and drug efflux [69,70]. Nonetheless, studies have reported that a cancer cell population that is resistant to chemotherapeutic treatment, to some extent, can be slightly more susceptible to PDT [70]. The recurrence and progression of colorectal cancer (CRC) has been linked to the presence of cancer stem-like cells (CSCs) that exhibit a high resistance to PDT [35].…”

“…Studies have reported that the size and shape of the NPs that are utilized in PDT can generally affect their interactions with biological barriers and tumour microenvironments, and subsequently compromise their accumulation via the EPR effect [84] In this sense, smaller sized NP-PS delivery vessels are possibly desirable in order to further improve the penetration of PSs into tumours [48]. Moreover, the introduction of modifications to the surface of the nanoparticles, such as polyethylene glycol (PEG) could shield them from opsonisation and aggregation and prolong their circulation time [69,70]. Polyethylene glycol (PEG) is one of the commonly utilized ligands in the designing of multifunctional NPs for PS drug delivery [69,70].…”

“…Moreover, the introduction of modifications to the surface of the nanoparticles, such as polyethylene glycol (PEG) could shield them from opsonisation and aggregation and prolong their circulation time [69,70]. Polyethylene glycol (PEG) is one of the commonly utilized ligands in the designing of multifunctional NPs for PS drug delivery [69,70]. For instance, Ryu et al [85] reported the use of nanophotosensitisers that were composed of methoxy poly(ethylene glycol) (MePEG) and Ce6 with a small diameter of less than 100 nm in the Ce6-mediated PDT treatment of colon cancer cells [85].…”