Nanotherapeutics for the Treatment of Hepatocellular Carcinoma

Preclinical Studies on Nanocarrier-Mediated Delivery of Radiosensitizing Agents to Brain and Pancreatic Cancer with a Future Projection to Liver Cancer

Author(s): Peter Sminia*, Pei Pei Che, Ben J. Slotman and Elisa Giovannetti

Pp: 316-332 (17)

DOI: 10.2174/9789815039740122010010

* (Excluding Mailing and Handling)

Abstract

Radiotherapy is one of the primary treatment modalities in oncology. The
therapeutic effectiveness of irradiation is dependent on the balance between the tumor
control probability (TCP) and the normal tissue complication probability (NTCP), i.e.,
the induction of side effects. Combination treatment of irradiation with chemotherapy
targeted to a tumor or using immune-modulating agents could significantly benefit
from nanotechnology strategies, allowing localized delivery of therapeutic compounds
to the irradiated tumor volume. When used in combination with irradiation, drugs
should be selected on their interaction with the 6 R’s, the six Hallmarks of
Radiobiology, to sensitize the radiation effect on the molecular, cellular, and tissue
level, and in addition to that, positively impact the TCP/NTCP balance. This chapter
presents and discusses preclinical data on the combination of irradiation and
nanocarrier-mediated delivery of drugs in the brain, pancreatic, and liver cancer. Before
implementation into the clinical practice, nanotechnology demands further technical
and biological studies on drug loading efficacy, drug release, cellular and tissue uptake,
biodistribution, tumor-targeting methods, and administration routes to the patient.
Notwithstanding those challenges, the combination of local radiotherapy with tumortargeted
nanocarrier-delivered radiosensitizers, as well as the use of radiosensitizing
nanoparticles, are exciting developments with a great clinical prospect.


Keywords: Blood-brain barrier, Binimetinib, Brain tumour, Curcumin, GBM, Hallmarks of radiobiology, Hepatocellular carcinoma, Immune-modulating agents, Nanocarriers, Oncology, Pancreatic cancer, Radiosensitization, Radiotherapy, Six R ’s, Therapeutic agents.

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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1465
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1478
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51817477 and j.to_ip >=51817477 )) and ((j.from_date <= 1739988355 and j.to_date >= 1739988355 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16547) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51817477 and j.to_ip >=51817477 )) and ((j.from_date <= 1739988355 and j.to_date >= 1739988355 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16547) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51817477 and j.to_ip >=51817477 )) and ((j.from_date <= 1739988355 and j.to_date >= 1739988355 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16547)
      790μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 3312 and `b`.`banner_from_date` <= 1739988355 and `b`.`banner_to_date` >= 1739988355 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.11msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 3312
      • 3: 1739988355
      • 4: 1739988355
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='17bdb8db2899c7a3e177d3820b909b46'
      270μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    15Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        0FPU2XlYkxlFF04c1VcHP3sutt8zRFlSM4WHUxoI
        uc_cart_id
        17bdb8db2899c7a3e177d3820b909b46
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/16547" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/16547
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6InJpNWhtcXI3bU9odGxDNzY5c1dDZUE9PSIsInZhbHVlIjoieUFmSDR1RGlUWGxLc0I1elNQKzNkOW1WVEo4WCtBNklBR3Q1RFQ4ZGY0TT0iLCJtYWMiOiI2Njk0MDZlY2NiZjMzYWJjOWQ4YzllOTI0NWIyZGRiNzc1OGEwMzI5Zjk5Mzg4NGU3ZjcxMDg0YzEwNWFjMDMyIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6InJpNWhtcXI3bU9odGxDNzY5c1dDZUE9PSIsInZhbHVlIjoieUFmSDR1RGlUWGxLc0I1elNQKzNkOW1WVEo4WCtBNklBR3Q1RFQ4ZGY0TT0iLCJtYWMiOiI2Njk0MDZlY2NiZjMz" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Wed, 19 Feb 2025 18:05:55 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImNBeTdPYy9wNzhuenVtOVVEZ0dpZ3c9PSIsInZhbHVlIjoiYThOZ3Rma3BrQ0IybjQ2MWRodGNlZFNWeWtKZXVkT3NjU1NHSDd1b3JRVGQ5Y3k2aGZsZjY5ZVB0UUVVU3Q5SnBqZVVyQmpHUnJpOWRGWHMwTXduKzZydlRDcUVZRitHbTdwSjU5T2huaEFxM3dCUGx5MEt0K0hmdFB1eWRSRXciLCJtYWMiOiI1MWZiY2Q2MTI0MTFjNmEzZmIxZmExYjY2ZmE2YjE0Y2U4ZjRhN2M4MGY4OGZkYzA0YjEwZDlkMzRjZGJiOWM2IiwidGFnIjoiIn0%3D; expires=Sat, 22 Feb 2025 06:05:55 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6ImNBeTdPYy9wNzhuenVtOVVEZ0dpZ3c9PSIsInZhbHVlIjoiYThOZ3Rma3BrQ0IybjQ2MWRodGNlZFNWeWtKZXVkT3NjU1NHSDd1b3JRVGQ5Y3k2aGZsZjY5ZVB0UUVVU3Q5SnBqZVVyQ" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlJjei9LSitZbUYraGJNT3Z5U3BGUlE9PSIsInZhbHVlIjoicG5Hb0pJMThkeENPbWFiUzFZdUszWkVOZlJZRGpDVkQ0QXJBUWVHMlZDM2c4M1paUUdkQ2E0dk9UMEhjSGQvT2FMOEFKWFFGU0JTMktNa3h2dmF3b1FWSXVGMjdxSzdWYkdlTEFOZVpsb0hJcElFWkg4Zk8zcFg0YXErUTlNU2YiLCJtYWMiOiJmMjMyZTJlODRkOTJkY2IwODZiN2Y2N2ZiYmU1YWY5YWNjMjlmOGI2ZjQyYWY5OTkyMDc1Y2ZhNmY5N2EwYjBmIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IlJjei9LSitZbUYraGJNT3Z5U3BGUlE9PSIsInZhbHVlIjoicG5Hb0pJMThkeENPbWFiUzFZdUszWkVOZlJZRGpDVkQ0QXJBUWVHMlZDM2c4M1paUUdkQ2E0dk9" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImNBeTdPYy9wNzhuenVtOVVEZ0dpZ3c9PSIsInZhbHVlIjoiYThOZ3Rma3BrQ0IybjQ2MWRodGNlZFNWeWtKZXVkT3NjU1NHSDd1b3JRVGQ5Y3k2aGZsZjY5ZVB0UUVVU3Q5SnBqZVVyQmpHUnJpOWRGWHMwTXduKzZydlRDcUVZRitHbTdwSjU5T2huaEFxM3dCUGx5MEt0K0hmdFB1eWRSRXciLCJtYWMiOiI1MWZiY2Q2MTI0MTFjNmEzZmIxZmExYjY2ZmE2YjE0Y2U4ZjRhN2M4MGY4OGZkYzA0YjEwZDlkMzRjZGJiOWM2IiwidGFnIjoiIn0%3D; expires=Sat, 22-Feb-2025 06:05:55 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6ImNBeTdPYy9wNzhuenVtOVVEZ0dpZ3c9PSIsInZhbHVlIjoiYThOZ3Rma3BrQ0IybjQ2MWRodGNlZFNWeWtKZXVkT3NjU1NHSDd1b3JRVGQ5Y3k2aGZsZjY5ZVB0UUVVU3Q5SnBqZVVyQ" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlJjei9LSitZbUYraGJNT3Z5U3BGUlE9PSIsInZhbHVlIjoicG5Hb0pJMThkeENPbWFiUzFZdUszWkVOZlJZRGpDVkQ0QXJBUWVHMlZDM2c4M1paUUdkQ2E0dk9UMEhjSGQvT2FMOEFKWFFGU0JTMktNa3h2dmF3b1FWSXVGMjdxSzdWYkdlTEFOZVpsb0hJcElFWkg4Zk8zcFg0YXErUTlNU2YiLCJtYWMiOiJmMjMyZTJlODRkOTJkY2IwODZiN2Y2N2ZiYmU1YWY5YWNjMjlmOGI2ZjQyYWY5OTkyMDc1Y2ZhNmY5N2EwYjBmIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IlJjei9LSitZbUYraGJNT3Z5U3BGUlE9PSIsInZhbHVlIjoicG5Hb0pJMThkeENPbWFiUzFZdUszWkVOZlJZRGpDVkQ0QXJBUWVHMlZDM2c4M1paUUdkQ2E0dk9" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "0FPU2XlYkxlFF04c1VcHP3sutt8zRFlSM4WHUxoI" "uc_cart_id" => "17bdb8db2899c7a3e177d3820b909b46" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/16547" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-19 18:05:55GET/chapter/165471121917