Phase I Clinical Trial of Biodegradable Liposome-Gold Nanoparticles for

Photothermal Therapy of Oral Cancer

Origin of Proposal
Cancer is one of the most common causes of morbidity and mortality today. More than 20
million people all over the world are diagnosed with cancer; especially in developing countries.
Among the various types of cancer, oral cancer (ranked 6th) is the most fatal health complication
faced by mankind. Yearly more than 300,000 cases are reported for oral cancer of which 62 %
occur in developing countries. Indian population has oral cancer as most common type occurring
in men, and third most common in women (12.8 for men & 7.5 for women per 100,000 people
respectively). Tobacco use, unhealthy diets, alcohol consumption, inactive lifestyles, infection, etc
causes approximately 43 % of cancer deaths globally, among which tobacco use is world’s most
unavoidable cause. In India, tobacco consumption, may be in smoking (bidis and cigarettes) or
smokeless form (like chewing or use as mishri) mainly accounts (in ~95 % cases) for oral cancer.
Use of tobacco in various forms is increasing nowadays and estimated to cause 13 % of deaths in
India by 2020. The current treatment modalities available are surgery, chemotherapy, and
radiotherapy. Of these, surgery cannot remove all cancerous cells from the body completely.
Surgery unable to kill diminutive diseases such as tumor edges present around the tumor lumps
that further leads to secondary tumor. The patient should also possess minimal medical issues so
that they may tolerate the surgery and anesthesia at a time. Also, there is a higher chance of
systemic toxicity to healthy cells during conventional therapies. However, radiation therapy is
painless, but may lead to side effects such as nausea, vomiting or diarrhea, in early symptoms.
Subsequently, other side effects may develop, such as lymphedema, mouth problems, joint
problems, brain changes, infertility, in addition to secondary cancers. In spite of the favorable
outcome by currently used Immunotherapy based on antibodies (i.e. trastuzumab), acquires
significant resistance against numbers of patients with specific antigen positive tumors. There has
also been an unforeseen delay between diagnosis and treatment initiation that further leads to poor
patient acquiescence. Henceforth, there is an unmet need for the development of alternative
treatment approaches that can be effective in India in terms of its provision and outreach to
common people. Theranostic approaches for diagnosis as well as tumor-specific treatment by
therapeutic agents can be used to treat oral cancer.

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 In the trailing of therapies proficient of reducing undesired side effects and enhancing
efficacy, there has been growing interest in employing hyperthermia to attain these aims. The
intrinsic or extrinsic ER-mediated apoptosis can be achieved by low grade (43°C) and high grade
(45°C) hyperthermia. Gold (Au) is a multifunctional material that has been utilized for the
hypothermic medicinal effect. In spite of that, photothermal therapy (PTT) is a minimally invasive
therapeutic strategy in which photon energy from light is converted into heat in order to destroy
cancer cells. The use of near infrared (NIR) light (700-950 nm) in PTT is beneficial as NIR light
is minimally absorbed by the body tissue, thereby enabling NIR light to penetrate few centimeters
in the body. This avoids the infection-related complications that are commonly encountered after
surgery and circumvents the side effects from using toxic drugs in chemotherapy.
Gold nanoparticles (Au NPs) have been brought to the forefront of research in recent years
because of their facile synthesis, surface plasmon resonance, active surface for functionalization
(presence of thiol and amine groups), strongly enhanced and tunable optical properties as well as
excellent biocompatibility feasible for clinical settings. The non-radiative properties of Au NPs
have shown great potential in photothermal cancer therapy. A range of new approaches with Au
NPs are under progress. The first demonstration of gold nanoparticle (Au NPs) based photothermal
therapy was published in 2003 using silica gold nanoshells (Au NSs) by West, Halas, and co-
workers. Dickerson et. al demonstrated PTT using gold nano rods in 2006, followed by
development of Au Nano cages and its demonstration for photothermal destruction of cancer cells
was reported by Xia and co-workers in 2007.
Currently, AuroLase therapy, a type of PTT based on 150 nm silica-gold nanoshells (Au
NSs) that absorb NIR light, produce heat, and are coated with polyethylene glycol (PEG), was
developed by Nanospectra Biosciences, Inc. and has been under clinical trials (ClinicalTrials.gov
Identifiers: NCT00848042 for refractory and/or recurrent tumors of the head and neck
(2008−2014), NCT01679470 for metastatic lung tumors (2012−2014), and currently recruiting
clinical NCT02680535 for localized prostate cancer (2016 until now). Please refer table 1.
However, Au NPs assisted PTT presents its own unique challenges, mainly the long-term
biological fate of Au NPs. The potential applications of Au NPs are endless, but their practical
value in nanomedicine is dependent upon their toxicity level. In all the above cases (and most other
photothermal experiments) the nanoparticles used are > 100 nm in size and hence their clearance
from the body will be slow as gold is nonbiodegradable. Clinical trials based on silica-gold NPs,

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 silica-gold nanoshells coated with PEG (AuroLase@) are under progress. Silica-gold
nanostructures can achieve the NIR absorbance, but most of the reported NPs are sizes of >100
nm which are non-biodegradable (D. Bechet et al, Trends Biotechnol., 2008).
Hence, we have developed biodegradable plasmon resonant liposome gold nanoparticles
(LiposAu NPs) capable of killing cancer cells through PTT. LiposAu NPs are biocompatible, with
100 % clearance rate. The long-term in vivo analysis also confirmed the bimodal (hepatobiliary
and renal) clearance of Au NPs. The pharmacokinetic study of LiposAu NPs was performed in a
small animal model indicated in situ enzymatic degradation into smaller particles in hepatocytes
and further getting cleared through the hepatobiliary and renal route.
Therefore, our biocompatible and biodegradable LiposAu NPs proved to be efficient
photothermal agents for photothermal therapy of cancer. The novel biodegradable LiposAu NPs
hold great promise to translate into clinics as a cancer Nanotheranostics.

A) Rational of the study supported by cited Literature*

Many organic and inorganic nanosystems are extensively researched for imaging and
treatment of cancer, but not all could satisfy the criteria for clinical or human use (FDA/DCGI
regulations). The most important factor determining the approval of such new systems is their
ability to get cleared from the body after killing cancer cells (without affecting normal cells).
According to the Food and Drug Administration (FDA) guidelines, any imaging agent
(administered into the body) should be capable of getting cleared completely from the body within
a reasonable period of time. Majority of the nanosystem lack either the efficacy to reach and kill
specific cancer cells or the ability to get cleared fast (renal clearance) after killing cancer cells. To
achieve renal clearance, the size of inorganic nanoparticles will have to be < 5.5 nm. Inorganic,
metal-containing nanoparticles less than 5.5 nm in size are capable of getting filtered through the
glomerular basement membrane (GBM), thereby serving as ideal candidates for imaging (with
renal route of clearance). Gold based materials deployed in PTT are generally larger than 20 nm
in size. Accumulation of such metallic nanoparticles in body could serve as a potential health risk.
In 2013, Melnik et al. reported the transfer of silver nanoparticles via placenta to the rat fetuses,
bringing out the gravity of risk involved in nanoparticle accumulation. Although many of such
materials could serve as efficient imaging agents, their larger size and non-degradable nature
prevents renal clearance, thus limiting their application in vivo. Hence, a multifunctional

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nanosystem capable of achieving good body clearance through both hepato-biliary and renal route
in addition to serving as effective agents for PTT is warranted.
Photothermal agents with excellent photothermal performance but relatively poor
degradability would raise long-term biosafety concerns. Building biodegradable PTT
nanomaterials with dynamic disassembly ability is a good strategy, enhancing the therapeutic
efficacy and avoiding nanotoxicity. However, such examples are rare. For example, nanoscale
coordination polymers (NCPs) with intrinsic biodegradability have been used for constructing one-
dimensional PTT nanomaterials, showing both good tumor accumulation and rapid renal
clearance. Multifunctional FeAP-NPs derived from fruit extracted anthocyanins has realized in
vivo disassembly and elimination although additional injection of iron chelators is required. Liu et
al. reported molybdenum oxide (MoOx) nanosheets with strong NIR absorbance for photothermal
ablation of tumor which can be degraded at physiological pH but remain relatively stable under an
acidic environment. Farokhzad et al. prepared PEG coated quantum dots (AMQDs) with excellent
photothermal conversion efficiency (45.5%) and also demonstrated a unique NIR-induced rapid
degradability, which would be degraded after treatments to profit their biological applications. The
intriguing optical and physicochemical properties of gold (Au) nanostructures endow them with
great potential in biomedical applications. Despite bio inert properties and biocompatibility of
metallic Au nanoparticles, the extremely long elimination half-lives limit their clinical translation.
To date, no effective strategies exist that enhance the metabolism and clearance of Au
nanoparticles in-vivo. Our group synthesized a liposome-gold nanoparticle hybrid system
(LiposAu NPs) that has multifunctional (imaging and therapeutic) capabilities. Since the core of
this nanohybrid system is made up of biodegradable lipid, the gold coating on the surface is capable
of splitting into smaller particles (≤ 5-8 nm) and achieving both hepato-biliary and renal clearance.
B) Hypothesis
Gold nanoparticles of size less than 8 nm could get cleared very fast but are not
photothermally active. The photothermally active gold nanosystems (Eg: Silica gold) are larger in
size (100 nm) and hence not suitable for faster (renal) clearance. Hence, we hypothesize LiposAu
NPs would be efficient nanotheranostic agents for photothermal therapy of oral cancer. The
biodegradable photothermally active gold based nanosystem that could be as efficient as non-
biodegradable ones in killing cancer cells. At the same time, they degrade themselves during the
process of photothermal therapy and achieve size range that is suitable for faster renal clearance.

4
 Our group is the first in the world to develop and demonstrate a biodegradable nanosystem
for photothermal treatment of cancer in-vivo. We have shown the in-vivo biodegradability and the
ability of the nanoparticles to undergo renal clearance owing to size reduction. We demonstrated
the in vivo pharmacokinetics and photothermal efficacy of biodegradable plasmon resonant
nanoparticles i.e., LiposAu NPs at the target site in a mouse breast tumor xenograft model.
At this stage, the first challenge for PTT in clinical use is the long-term biological behavior
of Au NPs and we have developed a biodegradable system that can overcome all the possibilities
of any systemic toxicity or clearance related issues. Hence a clinical trial using the nanosystem
Lipos Au will be more practical for the clinical translation of photothermal therapy. This system
will be more useful and has a greater potential of immediate translation as a stand-alone therapy
or adjuvant therapy or combinational therapy for achieving synergistic therapeutic efficacy against
oral cancer.
C) Key Questions
The following questions need to be addressed for the successful translation of LiposAu NPs
for PTT.
1. What will be the storage condition of LiposAu NPs and how long can it be stored?
2. What will be the therapeutic efficacy of LiposAu NPs in oral cancer?
3. What will be the LiposAu mediated post PTT clearance mechanism?
4. What will be the route of delivery of LiposAu NPs for PTT treatment of oral cancer?
5. How will the dose be evaluated?
6. Can imaging-guided PTT be performed using LiposAu NPs for oral cancer?
7. Will there any be side effects of LiposAu NPs?
8. What is the genotoxicity/immunotoxicity profile of LipsAu NPs?
9. Can LiposAu NPs be translated into Phase I trials?
Current Status of research and development in subject (both International and National
Status)
There are numerous reports demonstrating the in-vitro & in-vivo therapeutic efficacy of
various organic & inorganic nanosystems for PTT. Preclinical studies have shown the high degree
of safeness and efficacy of PTT in treating xenograft mice tumors, canine and feline patients. Some
of the nanosystems based on Au NPs are undergoing clinical trials too.

5
Clinical trials:
Currently, AuroLase therapy, a type of PTT based on 150 nm silica-gold nanoshells
(AuNSs) that absorb NIR light, produce heat, and are coated with polyethylene glycol (PEG), was
developed by Nanospectra Biosciences, Inc. and has been under clinical trials (ClinicalTrials.gov
Identifiers: NCT00848042 for refractory and/or recurrent tumors of the head and neck
(2008−2014), NCT01679470 for metastatic lung tumors (2012−2014), and currently recruiting
clinical NCT02680535 for localized prostate cancer (2016 until now)). Table 1, including the list
of ongoing/completed clinical trials of Au NPs

Table 1: Lists of clinical trials of Au NPs.

Nam Materials Conditi Applica Interve First Phas Recru Clinical

e on/dise tion ntion/tr Posted/ e itmen trials.go
ase eatmen Last t v
t Update Status Identifie
Posted r
NU- Spherical Gliosarc Targetin Laborat January Early Active NCT030
0129 Nucleic oma, g ory 13, 2017/ Phase , not 20017
Acid Recurre BCL2L Biomar August 22, 1 recruit
(SNA) Au nt 12 in ker 2018 ing
NPs Glioblas recurren Analysi
toma t s,
glioblas Pharma
toma cologica
l Study,
Targete
d
Therapy

6
Silica Si-Au Stable Nanoph Transpl January 5, NA Comp NCT012
- NPs Angina, otother antation 2011/June leted 70139
Gold Multive mal of 18, 2019
Nano ssel Therapy nanopar
parti Coronar of ticles
cles y Artery Atheros
Disease clerosis

Auro Silica-Au Neoplas Nanopa AuroSh February NA Active NCT026

Lase nanoshell ms of rticle ell 11, , not 80535
®
s coated the Directe particle 2016/Augu recruit
with PEG Prostate d Focal infusion st 28, 2019 ing
Therapy to ablate
for neoplas
Ablatio ms of
n of the
Prostate prostate
Tissue

CNM Au Healthy Clinical CNM- April 29, Phase Comp NCT027

-Au8 nanocryst Volunte Trial of Au8, 2016/June 1 leted 55870
al ers - CNM- Placebo 3, 2019
Male Au8 in
and Healthy
Female Male
and
Female
Volunte
ers

7
 Auro Silica-Au Head Therapy AuroLa February NA Comp NCT008
Lase nanoshell and in se 20, leted 48042
®
s coated Neck Refract Therapy 2009/Febr
with PEG Cancer ory uary 9,
and/or 2017
Recurre
nt
Tumors

Auro Silica-Au Metasta Primary AuroLa September NA Termi NCT016

Lase nanoshell tic Lung and/or se 6, 2012/ nated 79470
®
s coated Tumors Metasta Therapy November
with PEG tic Lung 3, 2016
Tumors

The results of a pilot study using silica gold nanoshells (GSN) for the treatment of prostate cancer
were recently reported by Naomi J. Halas group. This pilot device study reports feasibility and
safety data from 16 cases of patients diagnosed with low- or intermediate-risk localized prostate
cancer. GSN-mediated focal laser ablation was successfully achieved in 94% (15/16) of patients,
with no significant difference in International Prostate Symptom Score or Sexual Health Inventory
for Men observed after treatment. This treatment protocol was reported to be feasible and safe in
men with low- or intermediate-risk localized prostate cancer without serious complications or
deleterious changes in genitourinary function. No serious adverse events were reported (CTCAE
grade 3 or greater) during the procedure, and all patients were discharged home the day of the
procedure.This current study met its primary safety endpoint of the lack of any CTCAE grade 3 or
higher adverse events at 90 d follow-up. The endpoint of assessing efficacy: the ablation zones
were free of cancer in 60% (9/15) of patients at 3 mo and 86.7% (13/15) of patients at 12 mo. Prior
to human clinical trials, AuroLase-based PTT was utilized in the treatment of brain tumors in
orthotropic canines, and subsequent tumor ablation was observed after PTT.

8
 Ali et al. reported the treatment of spontaneous mammary gland tumors in cats and dogs
by directly injecting AuNRs into solid tumors (intratumoral injection, i.t.), followed by NIR
irradiation.After three sessions of treatments, efficient tumor regression was reported to be
achieved in all cases with no recurrence or metastasis. No toxic effects on the blood profile nor a
decrease in liver and kidney functioning afterwards were observed.(12)
Abdoon et al. also conducted & reported similar studies on dogs and cats with mammary
gland tumors. Results showed that the treated animals had complete remission (62.5% (10/16)),
partial remission (25% (4/16)), and significantly low remission (12.5% (2/16)), respectively.
London and co-workers used AuNR-PPTT to treat spontaneous neoplasia in dogs (carcinoma,
sarcoma, or mast cell tumors). The AuNRs were injected intravenously into seven canines 72 h
before using the 30 W, 808 nm NIR laser to irradiate the tumor mass. At the end of the study,
London and co-workers observed either partial or complete remission of tumors, and the overall
response rate was 28.6%.
The Relevance of Proposed Study
Scientific:
Gold nanoparticles (Au NPs) assisted PTT offers ample advantages in other types of cancer
treatments. First, Au NPs assisted PTT avoids the systematic side effects associated with
traditional cancer therapies, such as chemotherapy. The treatment mainly targets localized solid
tumors, with almost no damage to healthy tissues. Second, since PTT is a physical treatment, there
is no restriction on the types of tumors to be treated (non specific). Usually, different cancer types
have their own treatment drugs, and many develop resistance to particular drugs after a certain
time period and hence PTT could be a “universal” treatment for many types of cancer. However,
Au NP-assisted PTT presents its own unique challenges. The first issue concerns the biological
fate of Au NPs, especially in the long term. The potential applications of Au NPs are endless, but
their practical value in Nanomedicine is dependent upon their toxicity level.
We have addressed the above mentioned challenges by understanding the fate of the
biodegradable nanosystem, LiposAu NPs in-vivo. Our study involved understanding the
degradation dynamics of plasmon resonant LiposAu NPs under physiological condition. It was
observed that these particles were able to degrade by the enzymatic reaction into smaller particles
whose size range was ideal for renal excretion in addition to hepatobiliary route. The long-term in
vivo analysis also confirmed the bimodal clearance of these NPs. Their ability to generate a

9
massive amount of γH2A.X foci was a strong indicator of the mode of tumor ablation by DNA
double strand breaks. Applicability of such novel biodegradable hybrid nanoparticle system holds
great promise in cancer Nanotheranostics. This proposal has a greater relevance in the context of
a fully biodegradable nanosystem as a cancer Nanotheranostic.
Societal:
Cancer is one of the most common causes of morbidity and mortality today. Morethan 20
million people all over the world are diagnosed with cancer; especially in developing countries.
Early detection and treatment initiation is of prime importance in oral cancer. Surgery,
radiotherapy and chemotherapy have been the major treatment modalities in cancer, that have not
been effective in India due to lack of facilities and outreach (esp. in rural India that occupy majority
of the oral carcinoma population). In addition, due to invasiveness of surgery, ionizing radiation
in radiotherapy and the toxic side effects of chemotherapy, patient compliance appears to be poor.
Moreover, there has been an untoward delay between screening/confirmation and treatment
initiation that further leads to poor patient compliance. Chemotherapy and ionizing radiation may
have direct and indirect lethal effects on several organs. Although radiation therapy is painless, it
may cause other side effects such as nausea, vomiting, or diarrhea.
Looking into these fact, alternative treatment approaches, such as tumor-specific delivery
and activation of therapeutic agents to increase the efficacy of radiation therapy and hyperthermia
(often used to treat well-defined tumor volumes in the current clinical practices) can also be used.
The PTT can be a potential alternative and this technology will benefit all cancer patients suffering
from solid tumors like (oral, breast, and prostate cancer etc).
As India has a large number of cancer patients, affordable treatment becomes essential to
minimize the burden on healthcare. This technology can be adopted with minimal resource
settings, thereby providing affordable cancer care in urban as well as remote rural locations. The
project's goal of "identifying and treating cancer using smart biodegradable nanosystem" therefore
is of great societal relevance and is very prominent towards developing a healthy society.

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The Expected Outcome of Proposed Study
• An alternative approach for the treatment of cancer without any adverse side effects to
healthy tissues/organs.
• Clinical translation of an indigenously developed biodegradable nanosystem for the benefit
of the cancer patients.
• Au NPs will be used as CT contrast agents so it can be applicable for the diagnosis at early
stages and later stage (spread of cancer).
• Application of these biodegradable nanosystems as adjuvant and/or in combination with
existing therapies for greater therapeutic benefits.

The Preliminary Work done so far

The collaborating institutions IIT Bombay, ACTREC and IIT Hyderabad have developed
LiposAu NPs for PTT treatment of cancer. The research has been published in various reputed
journals. Below is list of work done so far on LiposAu NPs
• Synthesis & characterization of LiposAu NPs had been completed. The particle size was
measured to be 100−120 nm.
• Evaluated the photothermal properties of LiposAu NPs in vitro.
• Established the enzymatic and temperature mediated degradation of LiposAu NPs.
• In-vitro photothermal therapeutic efficacy of LiposAu NPs had been standardized.
• In-vivo PTT efficacy in HT1080 breast cancer xenograft model had been successfully
established. The complete ablation of tumor mass was achieved using 750 nm NIR laser
(650 mW) irradiation for 4 min with intratumoral injection of LiposAu NPs at dosage of
0.6 mg/kg body wt.
• Biodistribution, pharmacokinetics and clearance study of LiposAu NPs was completed
in a small animal model for 14 days period. The pharmacokinetics study of LiposAu NPs
performed in a small animal model indicates in situ degradation in hepatocytes and further
getting cleared through the hepato-biliary and renal route.
• Single and repeated dose toxicity of LiposAu NPs were completed in rats under GLP
condition. The single dose toxicity study of LiposAu NPs (up to 2.5 mg/kg of Au
concentration) was performed in 6-8 weeks rats (male and female) up to 14 days. We have
found that single dose i.v. administrated LiposAu NPs did not produce any adverse effect.

11
 Also, the repeated i.v. administration of LiposAu NPs at doses up to 1 mg/kg once in a week
for 12 weeks in 6-8 weeks rats (male and female) did not produce any toxicity.

For detail results please see Appendix I

Scope of the Application
Our goal is to transfer this photothermal therapy technology from bench to bed-side. We intend to
develop and optimize the effect of PTT in tumor tissues while keeping the surrounding organs
safe. Combining with real-time imaging, this will also enable us to validate the efficacy of this
treatment approach. When commercialized, this will be the first indigenously developed
biodegradable nanotheranostic agent for photothermal treatment of oral cancer in the world.

Objectives:
• Synthesis, characterization and scale-up the LiposAu NPs under GMP condition.
The LiposAu NPs will be synthesized using indigenously developed protocol and
characterized using TEM, SEM, DLS and Zeta. The photothermal transduction property
will also be evaluated.
• Stability Studies
o Accelerated stability: 40°C/75%RH for 6 Months
o Long term stability: 30°C/65%RH, 25°C/60%RH for 36 months
Assessment by – DLS and Zeta Potential, photothermal transduction.
• Determination of genotoxicity, immunotoxicity, carcinogenicity and reproductive
toxicity of LiposAu NPs
• Routine safety and lethality
This study is to determine a lethal dose of the formulation based on which a dose for acute
toxicity may be selected. A single rat will be administered a dose of 100 mg/kg body weight
and observed for 48 hours. The experiment will be continued in 2 ways:
o If the animal survives, a dose of 110 mg/kg body weight will be administered to
another animal followed by a dose up to 150 mg/kg body weight.
o If the animal does not survive a dose of 95 mg/kg till 50 mg/kg weight or still lower
will be administered to check for the survivability of the rat.

12
 All the animals will be observed for 48 hours before proceeding for the next dose. All
animals will be observed 1hr, 12hr, 1, 2, 3 and 7 days after injection for weight loss and
survival. LFT and KFT will be monitored for 7 days to evaluate safety.
• Determination of tolerated dosage
3 Groups of 6 rats will be administered formulations at ½, ¼ and 1/10th of MTD. Control
group will be given 5% glucose intravenously (iv). The tolerated dose is defined as the
dosage that caused neither death nor a significant change in body weight, renal function
and hepatic function 48h after intravenous administration
• Single Dose ADME Study (7 – Day) – Done in Metabolic Cages
Single dose of 1/10th dose of MTD will be administered through the tail vein of 6 rats and
housed in metabolic cages for 7 days. Body excreta including urine and feces will be
collected and analyzed by ICP-MS.
• Pilot Pharmacokinetics and Biodistribution Studies (ICP Analysis – 28 days)
60 Rats (200-250g) were administered with 1/10th of MTD of formulation and randomly
divided into 9 groups with 6 rats each (n=6). Each group would be assigned a pre-
determined time-point of sacrifice. The time points include:
o 6 Hours post administration
o 12 hours post administration
o 18 hours post administration
o 24 hours post administration
o Day 2 post administration
o Day 7 post administration
o Day 14 post administration
o Day 21 post administration
o Day 28 post administration
Plasma, spleen, liver, lung and kidney will be isolated, pat dried and weighed and assessed
for gold concentration using ICP – MS.
• Orthotopic/flank studies of Oral Squamous Cell Carcinoma.
Efficacy of LiposAu NPs to be used in PTT against cancer will be conducted in “SCC-VII
orthotopic or flank tumor model in C3H/HeN mice”. LiposAu NPs will be administered
intratumorally and irradiated with NIR laser.

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 o Dose Dependent
o Time Dependent
These parameters will be optimized for tumor regression.

• Regulatory filing for Phase I clinical trial

• Determination of pharmacokinetics and long-term toxicity of LiposAu NPs in
humans.
• Exploration and study of LiposAu NPs mediated laser ablation for oral cancer by
clinical trials.

Time line:
12 months • Scale up and stability study of LiposAu NPs
24 months • Determination of genotoxicity, immunotoxicity,
carcinogenicity and reproductive toxicity of LiposAu NPs
• Routine safety and lethality
• Determination of tolerated dosage
• Single Dose ADME Study (7 – Day) – Done in Metabolic
Cages
36 months • Pilot Pharmacokinetics and Biodistribution Studies (ICP
Analysis – 28 days)
• Orthotopic/flank studies of Oral Squamous Cell Carcinoma.
• Regulatory filing for Phase I clinical trial
48-60 months • Phase I clinical trial

14
Work plan:
Institute Roles
IIT Bombay • Scale up and stability study of LiposAu NPs
• Regulatory filing for Phase I clinical trial
AIIMS Delhi • Determination of genotoxicity, immunotoxicity,
carcinogenicity and reproductive toxicity of LiposAu NPs
• Routine safety and lethality
• Determination of tolerated dosage
• Single Dose ADME Study (7 – Day) – Done in Metabolic
Cages
• Pilot Pharmacokinetics and Biodistribution Studies (ICP
Analysis – 28 days)
• Orthotopic/flank studies of Oral Squamous Cell Carcinoma.

IIT Hyderabad • Complete in vitro characterizations of LiposAu NPs

ACTREC Navi • Phase I clinical trial
Mumbai

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