RECEPTOR-TARGETED LIPOSOME-ENCAPSULATED PHYCOCYANIN AND GOLD NANOPARTICLE FORMULATION FOR OPTIMIZED DUAL-MODE PDT AND PTT IN ORAL CANCER THERAPY

Abstract

ABSTRACT OF THE INVENTION The invention presents a novel formulation for dual-mode photodynamic and photothermal therapy designed for oral cancer treatment, incorporating liposome-encapsulated phycocyanin and gold nanoparticles as photosensitizers (CPC-AuNPs@Lips). A new treatment regime is presented using a low-concentration formulation at a low dosage of natural photosensitizers C-phycocyanin (C-PC) that shows improved pharmacokinetics and an effective method for photodynamic therapy (PDT). This novel formulation harnesses the benefits of phycocyanin, a natural pigment with strong near-infrared absorption, encapsulated in liposomes to enhance stability, solubility, and targeted delivery to tumor sites. Upon activation by specific light wavelengths, phycocyanin generates reactive oxygen species (ROS) to induce apoptosis in cancer cells. Gold nanoparticles complement this by converting nearinfrared light into localized heat, enhancing cancer cell ablation through photothermal effects. The fonnulation highlights targeting capabilities via cancer cell surface receptors, such as epidermal growth factor receptors (EGFR), to improve the specificity and effectiveness of treatment. Real-time imaging integrated into the formulation allows for precise monitoring and optimization of therapeutic outcomes. The inventive formulation can be utilized for photodynamic therapy (PDT) treannent regimes where photosensitizers are administered in one or more preselected doses, including those involving lowconcentration therapies. Specifically, when phycocyanin is used as the photosensitizer, it is formulated in a liposomal carrier system, with concentrations ranging from 0. I - 0.5 mg/ml. Gold nanoparticles are included to enhance the photothermal effect, with concentrations typically between 0.05 - 0.2 mg/ml. This formulation is designed to accumulate effectively in diseased tissue and provide a significant differentiation between cancerous and healthy tissues. The formulation's optimized composition allows for administration and activation within 24 hours, ensuring rapid therapeutic efficacy. This dual-mode approach not only integrates photodynamic and photothennal effects but also incorporates receptorspecific targeting and imaging, offering a comprehensive, efficient, and safe strategy for oral cancer therapy.

Specification

·Title of the invention
Receptor-Targeted Liposome-Encapsulated Phycocyanin and Gold Nanoparticle Formulation for
Optimized Dual-Mode PDT and PTT in Oral Cancer Therapy
FIELD OF INVENTION:
The present invention pertains to advanced cancer therapy techniques, specifically focusing on receptortargeted
photodynamic and photothermal treatments. This patent involves the development of a novel
formulation combining liposome-encapsulated phycocyanin and gold nanoparticles for optimized
therapeutic efficacy in oral cancer.
BACKGROUND OF THE INVENTION:
Oral cancer ranks as the sixth most common cancer worldwide, with a high mortality rate and lifetime
risk of about I in 59 for men and I in 139 for women. This highlights the critical need for early
detection and more effective treatments. Traditional methods such as surgery, radiation, and
chemotherapy often cause significant side effects and damage to healthy tissues due to their lack of
specificity. Recent advancements in liposome-based drug delivery systems present a promising solution
by targeting therapeutic agents directly to cancer cells, thereby reducing collateral damage and
improving treatment efficacy. Liposomes enhance drug stability, prevent degradation, and provide
controlled release, enabling more precise and personalized treatment options for oral cancer.
In recent years, advancements in targeted therapy have paved the way for innovative treatment
modalities that focus on enhancing specificity and reducing collateral damage. One such approach ;, the
use of photodynamic therapy (PDT) and photothermal therapy (PTT), which are emerging as promising
alternatives for cancer treatment. PDT utilizes photosensitizers that, upon activation by light, generate
reactive oxygen species (ROS) to induce cell death. PTT, on the other hand, employs nanoparticles to
convert light energy into localized heat, which can kill cancer cells. Combining these two therapies can
provide a synergistic effect, enhancing the overall efficacy of treatment.
The present invention introduces a novel fonnulation that integrates both PDT and PTT for the treatment
of oral cancer. This dual-mode therapy utilizes a formulation comprising liposome-encapsulated
phycocyanin and gold nanoparticles (CPC-AuNPs@Lips). Phycocyanin, a natural pigment with strong
near-infrared absorption properties, is encapsulated in liposomes to improve its stability, solubility, and
targeted delivery to tumor tissues. When exposed to specific wavelengths of light, phycocyanin
generates ROS, leading to apoptosis of cancer cells. Concurrently, gold nanoparticles enhance the
formulation by converting near-infrared light into localized heat, thus amplifying the photothermal
effect to further kill cancerous tissues.
The integration of these components into a single formulation not only optimizes the therapeutic effects
but also addresses several limitations of existing treatments. Liposomal encapsulation of phycocyanin
ensures efficient delivery to cancer cells while minimizing exposure to healthy tissues. The inclusion of
gold nanoparticles enhances the therapeutic efficacy through localized heating, which complements
ROS-mediated cell destruction from PDT. Additionally, the formulation utilizes targeting capabilities
via cancer cell surface receptors, such as epidermal growth factor receptors (EGFR), to improve the
specificity of treatment.
treatment progress and optimization of therapeutic outcomes. This advanced approach ensures that the
formulation accumulates effectively in diseased tissues, differentiates between cancerous and healthy
tissues, and enables administration and activation within 24 hours, facilitating rapid and efficient
treatment when compared to currently available treatment methods.
BRIEF DESCRIPTION OF THE ORA WINGS:
The drawings for the patent titled "Receptor-Targeted Liposome-Encapsulated Phycocyanin and Gold
Nanoparticle Fonnulation for Optimized Dual-Mode PDT and PTT in Oral Cancer Therapy" include the
following elements:
Formulation Schematic: i) A detailed diagram showing the composition of the liposome-encapsulated
fonnulation. ii) Illustration of liposomes encapsulating phycocyanin and the distribution of gold
nanoparticles on the surface of the liposomes.
Receptor-Targeting Mechanism: i) Diagrams depicting how the fonnulation targets specific receptors
on oral cancer cells. ii) Illustration of the interaction between the receptor-targeted liposomes and the
cancer cell surface.
Dual-Mode Therapy Overview: i) Schematics showing the mechanisms of both Photodynamic
Therapy (PDT) and Photothennal Therapy (PTT) within the fonnulation. ii) Representation of how light
activates phycocyanin (PDT) and how gold nanoparticles generate heat (PTT).
Therapeutic Process: i) Visuals demonstrating the process of administering the formulation, including
how it is delivered to the tumor site.
Targeting and Activation: i) Diagrams illustrating the activation of phycocyanin and gold
nanoparticles in response to light exposure. ii) Visuals showing the therapeutic effects on cancer cells,
such as cell death or destruction.
These drawings provide a clear and detailed representation of the formulation, its targeting mechanism,
and its dual-mode therapeutic actions
DETAILED DESCRIPTION OF THE INVENTION:
The present invention introduces a novel formulation designed for advanced oral cancer treatment using
a dual-mode approach combining photodynamic therapy (PDT) and photothermal therapy (PTT). The
fonnulation incorporates liposome-encapsulated phycocyanin and gold nanopanicles to optimize
therapeutic outcomes. Phycocyanin, a natural pigment derived from cyanobacteria, is a potent
photosensitizer due to its strong near-infrared light absorption. Encapsulating phycocyanin in liposomes
enhances its stability, solubility, and targeted delivery to cancerous tissues. Gold nanoparticles are
included in the formulation to provide additional therapeutic benefits through photothermal effects.
These nanoparticles convert near-infrared light into localized heat, which aids in the thermal ablation of
cancer cells, complementing the photodynamic effects of phycocyanin.
The preparation of the formulation involves several key steps. Phycocyanin is encapsulated within
liposomes using techniques such as thin-film hydration or extrusion, with concentrations ranging from
0.1 to 0.5 mg/ml to ensure effective loading while maintaining stability. Gold nanoparticles are
synthesized to achieve an optimal size and shape for effective photothermal conversion and are
incorporated into the liposomes at concentrations between 0.05 and 0.2 mg/ml. The liposomes are
designed to release their contents upon activation by specific light wavelengths.
The mechanism of action involves two synergistic therapies. Upon exposure to specific wavelengths of
light, phycocyanin generates reactive oxygen species (ROS) that induce apoptosis in cancer cells, while
gold nanoparticles convert near-infrared light into heat, enhancing the thermal destruction of cancerous
tissues. The liposomes are surface-modified with ligands that specifically bind to cancer cell receptors,
such as epidermal growth factor receptors (EGFR), increasing the specificity and targeting of the
formulation to tumor sites.
The formulation also includes real-time imaging capabilities or utilizes inherent optical properties for
monitoring drug distribution and treatment efficacy. This allows for precise adjustments to treatment
parameters and improves overall outcomes. The formulation is administered in preselected doses,
allowing for activation within 24 hours, which ensures rapid and effective therapeutic effects.
This novel approach offers several significant advantages: enhanced targeting through receptor-specific
liposomal delivery, a synergistic dual-mode therapy combining PDT and PTT, and optimized
pharmacokinetics for precise dosing and monitoring. While primarily intended for oral cancer therapy,
the formulation has the potential to be adapted for other cancersyere receptor-targeted, dual-mode
phototherapy could be beneficial.
SUMMARY OF THE INVENTION:
The invention pertains to a novel therapeutic fonnulation designed for optimized dual-mode
photodynamic therapy (POT) and photothermal therapy (PTT) specifically targeting oral cancer. The
formulation integrates liposome-encapsulated phycocyanin (C-PC) and gold nanoparticles (AuNPs) as
key components to enhance therapeutic efficacy and precision.
Phycocyanin, a natural pigment derived from cyanobacteria, is incorporated into liposomes to improve
its stability, solubility, and targeted delivery. As a photosensitizer, phycocyanin absorbs near-infrared
light and generates reactive oxygen species (ROS) upon activation, which induces apoptosis in cancer
cells. Gold nanoparticles are included in the fonnulation to convert near-infrared light into localized
heat, thereby augmenting the photothermal effect and promoting the ablation of cancerous cells.
The liposomes are modified with targeting lie;Hnds that specifically bind to epidermal growth factor
receptors (EGFR) on cancer cell surfaces. This receptor-targeted approach ensures that the therapeutic
agents are preferentially delivered to tumor tissues, enhancing the specificity and effectiveness of the
treatment while minimizing damage to healthy tissues.
The formulation also incorporates real-time imaging capabilities or utilizes inherent optical properties to
monitor drug distribution and treatment efficacy dynamically. This allows for precise adjustment of
treatment parameters, improving therapeutic outcomes.
The invention provides a comprehensive treatment strategy where the formulation is administered in
preselected doses, including low-concentration therapies, and activated within 24 hours using specific
wavelengths of light. This rapid activation ensures immediate therapeutic effects and efficient
integration of both PDT and PTT modalities.
In summary, the invention offers a novel, targeted, duration for diagnosis and a dual-mode therapeutic
approach for oral cancer treatment that combines the benefits of receptor-targeted drug delivery,
photodynamic and photothermal effects, and real-time imaging for optimized therapeutic outcomes .

CLAIMS
CLAIM 1: The fonnulation of claim I, wherein the liposomes are surface-modified with targeting
ligands that specifically bind to epidermal growth ·factor receptors (EGFR) present on cancer cell
surfaces, thereby increasing the specificity and accumulation of the therapeutic agents in tumor tissues.
CLAIM 2: The formulation of claim 2, wherein the concentration of phycocyanin in the liposomes is
between 0.1 mg/ml and 0.5 mg/ml, ensures optimal therapeutic efficacy while maintaining stability.
CLAIM 3: The formulation of claim 3, wherein the concentration of gold nanoparticles in the liposomes
is between 0.05 mg/ml and 0.2 mg/ml, achieving effective photothennal conversion.
CLAIM 4: The !ormulation of claim 4, further comprising real-time imaging agents or utilizing inherent
optical properties .of the formulation to enable dynamic monitoring of drug distribution and treatment
efficacy during therapy.
CLAIM 5: A method of claim 5 for treating oral cancer, comprising:
a) Administering the fonnulation of any of the preceding claims to a patient, where the formulation is
provided in preselected doses, including low-concentration therapies, for effective PDT and PTT;
b) Activating the formulation using specific wavelengths of light to induce PDT through the generation
of reactive oxygen species (ROS) by phycocyanin and PTT through localized heat from gold
nanoparticles.
CLAIM 6: The method of claim 6, wherein the fonnulation is administered and activated within 24
hours of administration, enables rapid therapeutic response and integrated PDT and PTT effects.
CLAIM 7: The formulation of claim 7, wherein the liposomes are engineered to release their
encapsulated contents upon exposure to specific wavelengths of light, ensuring targeted therapeutic
action and accumulation in cancerous tissues.
CLAIM 8: The formulation of claim 8, wherein the liposomes are prepared using techniques selected
from thin-film hydration, extrusion, or other suitable encapsulation methods to ensure stable and
effective delivery of phycocyanin and gold nanoparticles.
CLAIM 9: A therapeutic kit of claim 9 for oral cancer treatment, comprising:
a) The formulation of the above preceding claims;
b) Instructions for the administration, activation·, and monitoring of the formulation, including details
on dosing, light activation parameters, and imaging techniques for optimized PDT and PTT treatment.

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