The clinical need
for photodynamic therapy (PDT) has
been growing
for several decades. Notably, PDT is often used in oncology to treat
a variety of tumors since it is a low-risk therapy with excellent
selectivity, does not conflict with other therapies, and may be repeated
as necessary. The mechanism of action of PDT is the photoactivation
of a particular photosensitizer (PS) in a tumor microenvironment in
the presence of oxygen. During PDT, cancer cells produce singlet oxygen
(1O2) and reactive oxygen species (ROS) upon
activation of PSs by irradiation, which efficiently kills the tumor.
However, PDT’s effectiveness in curing a deep-seated malignancy
is constrained by three key reasons: a tumor’s inadequate PS
accumulation in tumor tissues, a hypoxic core with low oxygen content
in solid tumors, and limited depth of light penetration. PDTs are
therefore restricted to the management of thin and superficial cancers.
With the development of nanotechnology, PDT’s ability to penetrate
deep tumor tissues and exert desired therapeutic effects has become
a reality. However, further advancement in this field of research
is necessary to address the challenges with PDT and ameliorate the
therapeutic outcome. This review presents an overview of PSs, the
mechanism of loading of PSs, nanomedicine-based solutions for enhancing
PDT, and their biological applications including chemodynamic therapy,
chemo-photodynamic therapy, PDT–electroporation, photodynamic–photothermal
(PDT–PTT) therapy, and PDT–immunotherapy. Furthermore,
the review discusses the mechanism of ROS generation in PDT advantages
and challenges of PSs in PDT.
Topical administration of anti-cancer drugs along with
photodynamically
active molecules is a non-invasive approach, which stands to be a
promising modality for treating aggressive cutaneous melanomas with
the added advantage of high patient compliance. However, the efficiency
of delivering drugs topically is limited by several factors, such
as penetration of the drug across skin layers at the tumor site and
limited light penetrability. In this study, curcumin, an active anti-cancer
agent, and chlorin e6, a photoactivable molecule, were encapsulated
into lipidic nanoparticles that produced reactive oxygen species
(ROS) when activated at 665 nm by near-infrared (NIR) light. The optimized
lipidic nanoparticle containing curcumin and chlorin e6 exhibited
a particle size of less than 100 nm. The entrapment efficiency for
both molecules was found to be 81%. The therapeutic efficacy of the
developed formulation was tested on B16F10 and A431 cell lines via
cytotoxicity evaluation, combination index, cellular uptake, nuclear
staining, DNA fragmentation, ROS generation, apoptosis, and cell cycle
assays under NIR irradiation (665 nm). Co-delivering curcumin and
chlorin e6 exhibited higher cellular uptake, better cancer growth
inhibition, and pronounced apoptotic events compared to the formulation
having the free drug alone. The study results depicted that topical
application of this ROS-generating dual-drug-loaded lipidic nanoparticles
incorporated in SEPINEO gel achieved better permeation (80 ±
2.45%) across the skin, and exhibited the improved skin retention
and a synergistic effect as well. The present work introduces photo-triggered
ROS-generating dual-drug-based lipidic nanoparticles, which are simple
and efficient to develop and exhibit synergistic therapeutic effects
against cutaneous melanoma.
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